The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index; 2 of the 23 sources its claims cite were checked for support.
Interleukin 6 Is Important for Survival After Partial Hepatectomy in Mice
Open accessAbstract
The response to partial hepatectomy (PH) is impaired in interleukin 6 (IL–6)–deficient mice. IL–6 is well known for its role in the induction of the acute phase (AP) response, and the impairment of this response after surgery and hepatectomy could explain the defective hepatocyte regeneration. In addition, it was proposed that IL–6 has an important role in stimulating the reentry of quiescent cells into the cell cycle within the first 2 to 4 hours after PH. To further analyze the role for IL–6, we performed two third hepatectomies in wild–type mice, in IL–6 knockout (KO) mice, and in IL–6 KO mice that were treated 30 minutes before surgery with intravenous (IV) (short acting) or subcutaneous (SC) (long acting) injections of recombinant IL–6. The high postoperative mortality of IL–6–deficient mice could be completely prevented by SC, but not by IV IL–6 treatment, showing the requirement of a sustained action of IL–6. However, there is a subset of IL–6 KO mice that survives a PH in good health even without IL–6 treatment. When we analyzed these mice, we found an intact liver regeneration and no indication of a block in cell cycle reentry. We conclude that the major role of IL–6 is the induction of an adaptive response to PH that ensures body homeostasis and survival.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In IL-6-deficient mice, partial hepatectomy causes high mortality that can be rescued by subcutaneous but not intravenous IL-6, indicating that sustained IL-6/STAT3-dependent acute-phase signaling is required for survival. Surviving IL-6 knockout mice still regenerate liver mass through hepatocyte proliferation, with delayed cyclin D1/c-myc induction and compensatory cell-cycle mechanisms.
Key findings
- Seven-day survival after partial hepatectomy was 86% in wild-type controls versus 17% in untreated IL-6 knockout mice; subcutaneous IL-6 restored survival to 86%, whereas intravenous IL-6 did not rescue survival.
- Subcutaneous IL-6 produced later peak serum concentrations and prolonged STAT3 activation, and induced the acute-phase protein SAP; intravenous IL-6 did not induce SAP above constitutive levels.
- In IL-6 knockout mice that survived in good health, liver mass restoration was similar to wild-type mice; BrdU incorporation was lower at 40 hours after PH (17% vs. 27% nuclei stained) but not different at 48 or 60 hours.
- Cyclin D1 and c-myc up-regulation were absent early in IL-6 knockout livers, but cyclin E-CDK2 association was unchanged and cyclin D3-CDK6 lacked the inhibitor p27^Kip1 at 36 and 48 hours, suggesting compensatory cell-cycle progression.
Methods
- Eight- to 12-week-old IL-6-deficient mice and C57Bl/6J controls underwent two-thirds partial hepatectomy; IL-6 knockout mice received 500 ng/g body weight recombinant human IL-6 subcutaneously or intravenously 30 minutes before surgery.
- Survival was observed for 7 days; liver regeneration was assessed by liver weight, hepatocyte counts, and in vivo BrdU labeling at time points after PH.
- Molecular analyses included serum IL-6 ELISA, STAT3 electrophoretic mobility shift assay, Northern and Western blots for SAP, and Western blot/immunoprecipitation for cyclins D1/D2/D3, c-myc, CDK2/CDK6, and p27.
Limitations
- The paper states that loss-of-function models such as IL-6-deficient mice cannot distinguish between different functions of a cytokine because all functions are lost simultaneously.
- The paper notes that its BrdU results differ from prior work possibly because it excluded sick mice from regeneration analysis or because of different mouse strains.
- Evident from the text: regeneration and cell-cycle analyses were restricted to the subset of IL-6 knockout mice that survived in good health, while sick mice were euthanized and excluded, so findings may not represent all IL-6-deficient mice after PH.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
2 of 23 cited sources checked · 0 supported · 0 flagged · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“From experiments with cyclin D1 KO mice, it is known that other D type cyclins can functionally replace cyclin D1 in most tissues.17,18”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Cell Cycle Analysis During Liver Regeneration in IL-6 KO Mice.
What the sources say
- Not checked — no full text of the sourcecites [17] Sicinski, 1995, Cell source
- Partly supportedcites [18] Fantl, 1995, Genes Dev sourceExperimental — accuracy not yet measured
The Discussion (page not provided) proposes that D-type cyclins might substitute for one another, but also offers alternative signaling pathways as an explanation and says further experiments are needed to distinguish them. It therefore does not establish that other D-type cyclins functionally replace cyclin D1 in most tissues. (LLM, conf=0.87)
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Simi-lar results have been reported with a different strain of IL-6 -deficient mice.16”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Discussion
What the sources say
- Partly supportedcites [16] Sakamoto, 1999, Hepatology sourceExperimental — accuracy not yet measured
The “Sequential Liver Weight Before and After PH” section reports that liver-weight recovery was significantly impaired in IL-6-deficient mice at 48, 60, and 72 hours. The groups reached the same percentage of normal liver weight by 96 hours, so the claim holds for that endpoint but not for remnant liver growth throughout recovery. (LLM, conf=0.88)
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When we analyzed these mice, we found an intact liver regeneration and no indication of a block in cell cycle reentry.”
- Also stated in: § Abstract · plain
“Contrary to previously published results, we do not find a significant inhibition of hepatocyte proliferation in those IL-6deficient mice that survive PH.”
- Also stated in: § Liver Regeneration in IL-6 -Deficient Mice That Survive After PH. · plain
“Interestingly, IL-6 KO mice that survived in good health after PH showed a very similar regain of liver weight as controls (Fig. 3A).”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The IL-6 knockout mice that survive partial hepatectomy in good health are representative of all IL-6 knockout mice that survive partial hepatectomy.
- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When we analyzed these mice, we found an intact liver regeneration and no indication of a block in cell cycle reentry.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: The IL-6 knockout mice that survive partial hepatectomy in good health are representative of all IL-6 knockout mice that survive partial hepatectomy.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, there is a subset of IL-6 KO mice that survives a PH in good health even without IL-6 treatment.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Abstract
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is noteworthy that the induction of the AP protein SAP is observed only after SC, and not after IV IL-6 treatment.”
- Also stated in: § Discussion · plain
“Concentration of the AP protein SAP in the serum of mice after IV or SC injection of 500 ng/g bodyweight rhIL-6.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In agreement with this, the serum concentration of SAP was much more strongly up-regulated in mice after SC than after IV injection of IL-6 (Fig. 2D).”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > SC Injection of IL-6 Results in Prolonged STAT3 Activation and Induction of AP Proteins.
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Survival during the 7 days after surgery was 86% for controls and 17% for KO mice not treated with IL-6 (Fig. 1).”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Mortality After PH.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Rests on an assumption: IL-6 knockout mice and wild-type controls are comparable except for the IL-6 deficiency, including their genetic background.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found a strong induction of SAP 8 and 24 hours after SC injection of 500 ng/g bodyweight rhIL-6 in IL-6 KO mice.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > SC Injection of IL-6 Results in Prolonged STAT3 Activation and Induction of AP Proteins.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We show here, that in the subset of IL-6 KO mice that survive in good health after PH, liver regeneration takes place without the induction of cyclin D1.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 19
- Probably not a substantial claim. 9
- The quote only partly states this claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The high postoperative mortality of IL-6 -deficient mice could be completely prevented by SC, but not by IV IL-6 treatment, showing the requirement of a sustained action of IL-6.”
- Also stated in: § Abstract · plain
“SC, but not IV, IL-6 injections can protect IL-6deficient mice from excess mortality.”
- Also stated in: § Mortality After PH. · plain
“SC IL-6 treatment allowed 86% survival, whereas an IV injection could not rescue the IL-6 KO mice.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: IL-6 knockout mice and wild-type controls are comparable except for the IL-6 deficiency, including their genetic background.
- Also stated in: § Abstract · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that the high mortality observed in IL-6 KO mice could be corrected by SC, but not by IV IL-6 substitution.”
- Also stated in: § Discussion · plain
“SC injection of IL-6 resulted in survival of 86% (}), not different from the wild-type mice.The injection of the same amount of IL-6 into the tail vein could not improve survival of IL-6 KO mice (F).”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Discussion · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As shown in Fig. 5C and 5D, both cyclins are present in liver extracts, but neither of them is up-regulated during the G1 phase of the cell cycle.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Cell Cycle Analysis During Liver Regeneration in IL-6 KO Mice.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The IL-6 knockout mice that survive partial hepatectomy in good health are representative of all IL-6 knockout mice that survive partial hepatectomy.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“a complex we found free of the inhibitor p27 Kip1 during liver regeneration in IL-6 KO mice, but not in controls.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In IL-6 KO mice, cyclin D1 up-regulation remains undetectable in the first 48 hours and is up-regulated only later, at 72 hours and 96 hours (Fig. 5A).”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Cell Cycle Analysis During Liver Regeneration in IL-6 KO Mice.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The IL-6 knockout mice that survive partial hepatectomy in good health are representative of all IL-6 knockout mice that survive partial hepatectomy.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“SC IL-6 treatment allowed 86% survival, whereas an IV injection could not rescue the IL-6 KO mice.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Mortality After PH.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: IL-6 knockout mice and wild-type controls are comparable except for the IL-6 deficiency, including their genetic background.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The IV route resulted in a rapid but transient STAT3 activation that lasted 2 hours and was very weak after 4 hours.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > SC Injection of IL-6 Results in Prolonged STAT3 Activation and Induction of AP Proteins.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Indeed, peak concentrations were measured later (after 30 minutes vs. 10 minutes in IV-injected animals), and elevated IL-6 concentrations were found up to 4 hours after SC injections of 500 ng/g body weight rhIL-6 (Fig. 2A).”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > SC Injection of IL-6 Results in Prolonged STAT3 Activation and Induction of AP Proteins.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The cells look slightly larger in IL-6 KO mice, but are otherwise normal, without increased glycogen or fat content.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Liver Regeneration in IL-6 -Deficient Mice That Survive After PH.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The IL-6 knockout mice that survive partial hepatectomy in good health are representative of all IL-6 knockout mice that survive partial hepatectomy.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We found that 4.8% of the hepatocytes were binucleated in wild-type, and 5.8% in IL-6 KO mice, a difference that is not significant in our context.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Liver Regeneration in IL-6 -Deficient Mice That Survive After PH.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The IL-6 knockout mice that survive partial hepatectomy in good health are representative of all IL-6 knockout mice that survive partial hepatectomy.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After SC application, STAT3 remained strongly activated in the first 4 hours and was detectable in electrophoretic mobility shift assays for up to 8 hours (Fig. 2B).”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > SC Injection of IL-6 Results in Prolonged STAT3 Activation and Induction of AP Proteins.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Interleukin 6 (IL-6) was identified as the principal activator of STAT3, whereas tumor necrosis factor ␣ (TNF-␣) induces NFB.7,8”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Abstract
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesIt may state two separate claims as one.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Several of these induced genes are target genes of signal transducer and activator of transcription (STAT)3 and nuclear factor kappa B (NFB), two transcription factors that are activated early during liver regeneration.5,6”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Abstract
What the sources say
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Convincing evidence has been found that mitogenic signals for hepatocytes are transported in the blood 2,3 and that they induce a number of immediate early genes within 30 minutes after PH. 4”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Abstract
What the sources say
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“It was reported previously that IL-6 KO mice suffer from significant morbidity and mortality after PH and that the mice could be protected by SC injection of IL-6 30 minutes before surgery.7”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Mortality After PH.
What the sources say
- Not checked — no full text of the sourcecites [7] Cressman, 1996, Science source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The size of females was between 19 and 22 g, the size of males between 26 and 30 g, with no differences between KO animals and controls.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Animals.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In all experiments, controls were age-and sex-matched.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Animals.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“IL-6 KO mice do have fewer cells per area, but the difference is small and not compatible with a cell growth without division mechanism for restoration of liver mass in IL-6 KO mice.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Liver Regeneration in IL-6 -Deficient Mice That Survive After PH.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The IL-6 knockout mice that survive partial hepatectomy in good health are representative of all IL-6 knockout mice that survive partial hepatectomy.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“For this experiment, only mice in a good state of health after PH were analyzed.”
- Also stated in: § Liver Regeneration in IL-6 -Deficient Mice That Survive After PH. · plain
“The sick mice were spared from further experiments and euthanized and not used for further analysis.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Liver Regeneration in IL-6 -Deficient Mice That Survive After PH.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. The quote only partly states this claim.
- Also stated in: § Liver Regeneration in IL-6 -Deficient Mice That Survive After PH. · plain
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Cell cycle progression in the KO mice is somewhat slower, but finally takes place with the help of compensatory cyclin D3-CDK6 activation.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Cell Cycle Analysis During Liver Regeneration in IL-6 KO Mice.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The IL-6 knockout mice that survive partial hepatectomy in good health are representative of all IL-6 knockout mice that survive partial hepatectomy.
A claim is checked only against the cited paper’s full text, never its abstract, and none is available for its sources.
In the paper
“Cyclin D1 is up-regulated during liver regeneration after PH, 7,28,29”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Discussion
What the sources say
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“overexpression of cyclin D1 in hepatocytes promotes hepatocyte proliferation in vitro and in vivo.30,31”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Discussion
What the sources say
- Not checked — no full text of the sourcecites [30] Albrecht, 1999, Cell Growth Differ
- Not matchedcites [31] Nelsen, 2001, Cancer Res
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Furthermore, not only other D type cyclins, but also cyclin E can compensate for loss of D1. 19”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Cell Cycle Analysis During Liver Regeneration in IL-6 KO Mice.
What the sources say
- Not checked — no full text of the sourcecites [19] Bowe, 2002, Oncogene source
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We conclude that IL-6 is not required for liver cell proliferation, but has an essential role in recovery and survival after PH.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“it is obvious that compensatory mechanisms correct for the absence of c-myc and cyclin D1 induction, because liver cell proliferation clearly takes place in IL-6 KO mice.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The induction of the cell cycle proteins c-myc and cyclin D1 helps to promote liver cell proliferation, but is not a requirement for liver regeneration.”
§ Interleukin 6 is Important for Survival After Partial Hepatectomy in Mice > Discussion
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
IL-6 knockout mice and wild-type controls are comparable except for the IL-6 deficiency, including their genetic background.
“Eight-to 12-week old IL-6 -deficient mice (Jackson Laboratories, Bar Harbor, Maine; strain name B6; 129S2-Il6tm1Kopf; original reference 11) and C57Bl/6J mice (Biological Research Laboratories, Fu ¨llinsdorf, Switzerland) were used for the PH experiments.”
“In all experiments, controls were age-and sex-matched.”
The paper relies on this without support.
The IL-6 knockout mice that survive partial hepatectomy in good health are representative of all IL-6 knockout mice that survive partial hepatectomy.
“For this experiment, only mice in a good state of health after PH were analyzed.”
“The sick mice were spared from further experiments and euthanized and not used for further analysis.”
The paper relies on this without support.
The subset of IL-6 KO mice that survived in good health after partial hepatectomy is representative for assessing whether IL-6 is required for liver cell proliferation.
“We then focused on the analysis of liver regeneration in the subset of IL-6 KO mice that survived well and in apparently good health after PH.”
“The different results of the BrdU labeling experiments in our work compared with the previous report 7 could result from our exclusion of all sick mice for the analysis of liver regeneration after PH, or from the use of different mouse strains.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source doesn’t support the claim as written.
In the citing paper
“The IL-6-promoted liver regeneration was determined in IL-6 knockout mice, as the deletion of il6 impaired the compensatory proliferation of hepatocytes by reducing the downstream STAT3 activation [3, 4], thus promoting liver failure, which could be corrected by the treatment of IL-6.”
From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [3]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, the deletion of il6 gene also impairs the hepatocyte homeostasis and liver regeneration [3–5].”
From The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases (2024) · cites this paper as [3]
Experimental — accuracy not yet measuredThe check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Both PAMPs and LPS activate Kupffer cells, which subsequently synthesize two key cytokines—IL-6[45] and tumour necrosis factor-alpha (TNF-α)[46].”
From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [45]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Hepatocyte counting uses a different number of fields
MinorThe methods say three fields were counted per mouse, but the results say two to three fields were counted per mouse.
“Three high-power microscope fields of 0.31 mm 2 each were counted per mouse and time point.”
“in 8 control mice and 5 IL-6 KO mice (2 to 3 fields for each mouse) 96 hours after PH.”
Figure 5D identifies different CDK partners
MinorThe Figure 5D heading names CDK4, whereas its description says the extracts were immunoprecipitated with CDK6 antibodies.
“(D) Association of cyclin D3 with CDK4 and p27 Kip1 .”
“Extracts were immunoprecipitated with either CDK6 antibodies or with p27 antibodies, followed by Western blots with cyclin D3 specific antibodies.”
Citations
Cites
Acute-Phase Proteins and Other Systemic Responses to Inflammation
Gabay, C., & Kushner, I. (1999) · New England Journal of Medicine · doi:10.1056/nejm199902113400607 · Cited by 6,734
Michalopoulos, G. K., & DeFrances, M. C. (1997) · Science · doi:10.1126/science.276.5309.60 · Cited by 2,828
Impaired immune and acute-phase responses in interleukin-6-deficient mice
Kopf, M., Baumann, H., Freer, G., Freudenberg, M., Lamers, M., Kishimoto, T., Zinkernagel, R., Bluethmann, H., & Köhler, G. (1994) · Nature · doi:10.1038/368339a0 · Cited by 1,768
Gauldie, J., Richards, C. D., Harnish, D. C., Lansdorp, P. M., & Baumann, H. J. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.20.7251 · Cited by 1,635
Liver Failure and Defective Hepatocyte Regeneration in Interleukin-6-Deficient Mice
Cressman, D. E., Greenbaum, L. E., DeAngelis, R. A., Ciliberto, G., Furth, E. E., Poli, V., & Taub, R. (1996) · Science · doi:10.1126/science.274.5291.1379 · Cited by 1,538
Fausto, N. (2000) · Journal of Hepatology · doi:10.1016/s0168-8278(00)80412-2 · Cited by 1,022
Cyclin D1 provides a link between development and oncogenesis in the retina and breast
Sicinski, P., Donaher, J. L., Parker, S. B., Li, T., Fazeli, A., Gardner, H., Haslam, S. Z., Bronson, R. T., Elledge, S. J., & Weinberg, R. A. (1995) · Cell · doi:10.1016/0092-8674(95)90034-9 · Cited by 1,021
Yamada, Y., Kirillova, I., Peschon, J. J., & Fausto, N. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.4.1441 · Cited by 944
del Olmo, J. A., Peña, A., Serra, M. Á., Wassel, A., Benages, A., & Rodrigo, J. M. (2000) · Journal of Hepatology · doi:10.1016/s0168-8278(01)68827-5 · Cited by 895
Mice lacking cyclin D1 are small and show defects in eye and mammary gland development.
Fantl, V, Stamp, G., Andrews, A., Rosewell, I., & Dickson, C. (1995) · Genes & Development · doi:10.1101/gad.9.19.2364 · Cited by 691
Flagged first, then by citations
Research works printed but not linked: 5
- Higgins, 1931, Arch Pathol, 12, 188
- Rai, 1996, Am J Physiol, 270, g909
- Matsunami, 1992, Transplant Proc, 24, 1971
- Albrecht, 1999, Cell Growth Differ, 10, 397
- Nelsen, 2001, Cancer Res, 61, 8564
Cited by
Sorted by citations
Liver regeneration: from myth to mechanism
Taub, R. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1489 · Cited by 1,567
“As discussed below, however, some studies have questioned the proposed major role of IL-6 in the mitogenic response post-hepatectom”
ResultFausto, N., Campbell, J. S., & Riehle, K. J. (2006) · Hepatology · doi:10.1002/hep.20969 · Cited by 1,378
Increased Hepatic and Circulating Interleukin-6 Levels in Human Nonalcoholic Steatohepatitis
Wieckowska, A., Papouchado, B. G., Li, Z., Lopez, R., Zein, N. N., & Feldstein, A. E. (2008) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2007.01774.x · Cited by 597
The importance of immune dysfunction in determining outcome in acute liver failure
Antoniades, C. G., Berry, P., Wendon, J. A., & Vergani, D. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.08.009 · Cited by 364
“Numerous cytokines (TNF-a [178,179], IL-6 [180,181]) and growth factors (hepatocyte growth factor, epidermal growth factor [85]) are implicated in hepatic regeneration.”
BackgroundInfluentialRole of cytokines and chemokines in non-alcoholic fatty liver disease
Braunersreuther, V. (2012) · World Journal of Gastroenterology · doi:10.3748/wjg.v18.i8.727 · Cited by 359
Kern, L., Mittenbühler, M., Vesting, A., Ostermann, A., Wunderlich, C., & Wunderlich, F. (2018) · Cancers · doi:10.3390/cancers11010024 · Cited by 331
“Thus, IL-6 regulates, amongst others, acute phase responses and liver regeneration, resulting in dramatically increased IL-6 serum levels upon states of infection, inflammation, and liver damage [98,110,117].”
BackgroundFumagalli, S., Cara, A. D., Neb-Gulati, A., Natt, F., Schwemberger, S. J., Hall, J., Babcock, G. F., Bernardi, R., Pandolfi, P. P., & Thomas, G. (2009) · Nature Cell Biology · doi:10.1038/ncb1858 · Cited by 322
“Three days after rpS6 gene deletion, partial hepatectomy was performe”
Non-alcoholic fatty liver disease pathogenesis: The present and the future
Petta, S., Muratore, C., & Craxı̀, A. (2009) · Digestive and Liver Disease · doi:10.1016/j.dld.2009.01.004 · Cited by 287
“uman models of IR and NAFLD [122,134–140], and human studies ave founda linear relationshipbetweenbothserumandhepatic ILoliferator-activated receptor ; ROS, reactive oxygen species; SOCS, suppressor of”
BackgroundRegulation of liver regeneration by growth factors and cytokines
Böhm, F., Köhler, U. A., Speicher, T., & Werner, S. (2010) · EMBO Molecular Medicine · doi:10.1002/emmm.201000085 · Cited by 285
“Since various antagonists for growth factors or their receptors have been approved or are in clinical trials for the treatment of cancer, it will be interesting to determine whether these antagonists impair liver regeneration in humans.”
BackgroundCytokines, STATs and liver disease.
Gao, B. (2005) · PubMed · Cited by 274
Signal Transducer and Activator of Transcription 3 in Liver Diseases: A Novel Therapeutic Target
Wang, H., Lafdil, F., Kong, X., & Gao, B. (2011) · International Journal of Biological Sciences · doi:10.7150/ijbs.7.536 · Cited by 270
“[75] reported that IL-6-deficient mice had higher mortality after PHx but that the surviving IL-6-deficient mice had similar hepatocyte prolifera-”
BackgroundCarter-Kent, C. A., Zein, N. N., & Feldstein, A. E. (2008) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2007.01709.x · Cited by 204
“Previous concepts suggested that, in the liver, IL-6 has mainly a prosurvival and antiapoptotic action”
BackgroundHong, F., Radaeva, S., Pan, H., Tian, Z., Veech, R. L., & Gao, B. (2004) · Hepatology · doi:10.1002/hep.20400 · Cited by 202
Negative regulation of liver regeneration by innate immunity (natural killer cells/interferon-γ)
Sun, R., & Gao, B. (2004) · Gastroenterology · doi:10.1053/j.gastro.2004.08.055 · Cited by 187
Liver Regeneration after Hepatectomy and Partial Liver Transplantation
Yagi, S., Hirata, M., Miyachi, Y., & Uemoto, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218414 · Cited by 192
“STAT3 is a very important transcription factor involved in the induction of gene expression via cytokines [68,69].”
BackgroundPlatelets Promote Liver Regeneration in Early Period after Hepatectomy in Mice
Murata, S., Ohkohchi, N., Matsuo, R., Ikeda, O., Myronovych, A., & Hoshi, R. (2007) · World Journal of Surgery · doi:10.1007/s00268-006-0772-3 · Cited by 177
STAT proteins – Key regulators of anti-viral responses, inflammation, and tumorigenesis in the liver
Gao, B., Wang, H., Lafdil, F., & Feng, D. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.01.029 · Cited by 180
“[64]; however, several follow-up studies using IL-6 knockout mice generate conflicting data on the role of IL-6 on hepatocyte proliferation and liver regeneration [65–68].”
BackgroundRegulation of liver regeneration and hepatocarcinogenesis by suppressor of cytokine signaling 3
Riehle, K. J., Campbell, J. S., McMahan, R. S., Johnson, M. M., Beyer, R. P., Bammler, T. K., & Fausto, N. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20070820 · Cited by 161
Mohammed, F. F., Pennington, C. J., Kassiri, Z., Rubin, J. S., Soloway, P. D., Rüther, U., Edwards, D. R., & Khokha, R. (2005) · Hepatology · doi:10.1002/hep.20618 · Cited by 156
New insights into IL-6 family cytokines in metabolism, hepatology and gastroenterology
Giraldez, M. D., Carneros, D., Garbers, C., Rose-John, S., & Bustos, M. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00473-x · Cited by 156
Moh, A., Iwamoto, Y., Chai, G.-X., Zhang, S. S.-M., Kano, A., Yang, D. D., Zhang, W., Wang, J., Jacoby, J. J., Gao, B., et al. (2007) · Laboratory Investigation · doi:10.1038/labinvest.3700630 · Cited by 147
“However, increasing evidence suggests that IL-6 plays more important role in protection against liver injury, and only a minor role in liver regeneration.(5,6) Several transcription factors are activated shortly after PH or toxic liver injury, including NF-kB, signal transducer and activator of transcription 3 (STAT3)…”
Kong, L., Zhou, Y., Bu, H., Lv, T., Shi, Y., & Yang, J. (2016) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-016-0412-1 · Cited by 143
“In rodents, IL-6 is a progrowth factor required for hepatic regeneration and survival after partial hepatectomy [23, 24].”
Tsochatzis, E. A., Papatheodoridis, G., & Archimandritis, A. J. (2009) · Mediators of Inflammation · doi:10.1155/2009/831670 · Cited by 147
“Moreover, IL-6 has a hepatoprotective effect in ischaemic preconditioning models [60] and is important for survival after partial hepatectomy in mice [61].”
BackgroundHypoxia-Induced Endothelial Proliferation Requires Both mTORC1 and mTORC2
Li, W., Petrimpol, M., Molle, K. D., Hall, M. N., Battegay, E., & Humar, R. (2006) · Circulation Research · doi:10.1161/01.res.0000253094.03023.3f · Cited by 138
“A, Western blots showing total cell lysates of serum-deprived RAECs exposed to increasing duration of hypoxia (10 minutes to 24 hours) and probed for (numbering from top to bottom) (1) phosphorylated S6K-Thr389, (2) phosphorylated S6K-Thr389 in the presence of 20 nmol/L rapamycin, (3) total S6K, (4) phosphorylated Akt…”
BackgroundIL‐6 Trans‐signaling Controls Liver Regeneration After Partial Hepatectomy
Fazel Modares, N., Polz, R., Haghighi, F., Lamertz, L., Behnke, K., Zhuang, Y., Kordes, C., Häussinger, D., Sorg, U. R., Pfeffer, K., et al. (2019) · Hepatology · doi:10.1002/hep.30774 · Cited by 113
“Synergistic action of hepatocyte growth factor (HGF) and interleukin 6 (IL-6) controls the early regenerative phase after partial hepatectomy (PHX) by promoting both mitosis and survival of hepatocytes.(1-5) IL-6 binds to the IL-6 receptor (IL-6R), followed by dimerization of glycoprotein 130 (gp130), leading to JAK/S…”
BackgroundInfluentialConcerted Functions of Gab1 and Shp2 in Liver Regeneration and Hepatoprotection
Bard-Chapeau, E. A., Yuan, J., Droin, N. M., Long, S., Zhang, E. E., Nguyen, T. V., & Feng, G. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.02253-05 · Cited by 117
“from stress and infectious injury (5, 22, 47, 48, 56).”
BackgroundCytokines and STATs in Liver Fibrosis
Kong, X., Horiguchi, N., Mori, M., & Gao, B. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00069 · Cited by 115
“However, numerous studies demonstrated the hepatoprotective role of IL-6 against liver injury in spite of its pro-inflammatory effect (Blindenbacher et al., 2003; Wuestefeld et al., 2003).”
BackgroundArgast, G. M., Campbell, J. S., Brooling, J. T., & Fausto, N. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m405703200 · Cited by 104
Characterisation of a Novel Fc Conjugate of Macrophage Colony-stimulating Factor
Gow, D., Sauter, K. A. D., Pridans, C., Moffat, L., Sehgal, A., Stutchfield, B. M., Raza, S., Beard, P. M., Tsai, Y. T., Bainbridge, G., et al. (2014) · Molecular Therapy · doi:10.1038/mt.2014.112 · Cited by 102
Campbell, J. S., Riehle, K. J., Brooling, J. T., Bauer, R. L., Mitchell, C., & Fausto, N. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.4.2522 · Cited by 100
Finotto, S., Siebler, J., Hausding, M., Schipp, M., Wirtz, S. J., Klein, S., Protschka, M., Doganci, A., Lehr, H. A., Trautwein, C., et al. (2004) · Gut · doi:10.1136/gut.2003.018572 · Cited by 100
“These data are consistent with the recent demonstration of high IL-18 levels in the liver of patients with fulminant hepatic failure 30 42 and suggest that overexpression of IL-18 may cause substantial liver injury in vivo.”
Advances in Alcoholic Liver Disease
Beier, J. I., Arteel, G. E., & McClain, C. J. (2010) · Current Gastroenterology Reports · doi:10.1007/s11894-010-0157-5 · Cited by 98
“IL-6 is also involved in induction of an acute-phase response in the remaining liver tissue [ 44 ].”
BackgroundMarkers of liver regeneration—the role of growth factors and cytokines: a systematic review
Hoffmann, K., Nagel, A. J., Tanabe, K., Fuchs, J., Dehlke, K., Ghamarnejad, O., Lemekhova, A., & Mehrabi, A. (2020) · BMC Surgery · doi:10.1186/s12893-019-0664-8 · Cited by 94
IL-22 is involved in liver regeneration after hepatectomy
Ren, X., Hu, B., & Colletti, L. M. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00075.2009 · Cited by 109
“It is well documented that mice deficient in IL-6 regenerate their livers more slowly than normal animals after a variety of injuries and that stat-3 binding is also decreased in these animals (3, 19).”
BackgroundT cell-derived lymphotoxin regulates liver regeneration
Tumanov, A. V., Koroleva, E. P., Christiansen, P. A., Khan, M. A., Ruddy, M. J., Burnette, B., Papa, S., Franzoso, G., Nedospasov, S. A., Fu, Y., et al. (2009) · Gastroenterology · doi:10.1053/j.gastro.2008.09.015 · Cited by 89
Marshall, K. M., He, S., Zhong, Z., Atkinson, C., & Tomlinson, S. (2014) · The Journal of Experimental Medicine · doi:10.1084/jem.20131902 · Cited by 86
“IL-6 expression is dependent on TNF-induced NF-B activation, and IL-6–induced activation of STAT3 plays a role in cell cycle progression (Cressman et al., 1996; Yamada et al., 1997; Li et al., 2002; Blindenbacher et al., 2003).”
BackgroundMarkiewski, M. M., DeAngelis, R. A., & Lambris, J. D. (2005) · Molecular Immunology · doi:10.1016/j.molimm.2005.06.019 · Cited by 89
“Some recent studies have emphasized the hepatop ive role of IL-6 more strongly than its mitogenic activ Blindenbacher et al., 2003; Sakamoto et al., 1999; Wu eld et al., 2003).”
BackgroundThe double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases
Wang, M.-J., Zhang, H.-L., Chen, F., Guo, X.-J., Liu, Q.-G., & Hou, J. (2024) · Experimental Hematology & Oncology · doi:10.1186/s40164-024-00527-1 · Cited by 84
Impact of interleukin-6 classic- and trans-signaling on liver damage and regeneration
Drucker, C., Gewiese, J., Malchow, S., Scheller, J., & Rose-John, S. (2010) · Journal of Autoimmunity · doi:10.1016/j.jaut.2009.08.003 · Cited by 83
Role for the endoplasmic reticulum stress sensor IRE1α in liver regenerative responses
Liu, Y., Shao, M., Wu, Y., Cheng, Y., Jiang, S., Liu, J., Dai, J., Liu, Y., Li, J. X., Jia, W., et al. (2014) · Journal of Hepatology · doi:10.1016/j.jhep.2014.10.022 · Cited by 86
“For instance, animal model studies have established the importance of interleukin 6 (IL-6) in stimulating liver regeneration after partial hepatectomy (PH) or during hepatotoxin carbon tetrachloride (CCl4)-induced injury [7–10].”
BackgroundTeoh, N., Field, J., & Farrell, G. C. (2006) · Journal of Hepatology · doi:10.1016/j.jhep.2006.01.039 · Cited by 78
da Silva, C. G., Studer, P., Skroch, M., Mahiou, J., Minussi, D. C., Peterson, C. R., Wilson, S. W., Patel, V. I., Ma, A., Csizmadia, E., et al. (2013) · Hepatology · doi:10.1002/hep.26197 · Cited by 77
Advances in the regulation of liver regeneration
Jia, C. (2011) · Expert Review of Gastroenterology & Hepatology · doi:10.1586/egh.10.87 · Cited by 75
Lee, J. K., Bettencourt, R., Brenner, D. A., Le, T., Barrett-Connor, E. L., & Loomba, R. S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034218 · Cited by 74
“In rodents, IL-6 is a pro-growth factor required for hepatic regeneration and survival after partial hepatectomy [25,26].”
BackgroundNaseem, S., Hussain, T., & Manzoor, S. (2018) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2018.01.002 · Cited by 72
IL-6 modulates hepatocyte proliferation via induction of HGF/p21cip1: Regulation by SOCS3
Sun, R., Jaruga, B., Kulkarni, S., Sun, H., & Gao, B. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.10.171 · Cited by 73
Przybyt, E., Krenning, G., Brinker, M. G. L., & Harmsen, M. C. (2013) · Journal of Translational Medicine · doi:10.1186/1479-5876-11-39 · Cited by 69
“Furthermore, IL-6 facilitates healing of damaged skeletal muscle through mitotic stimulation of muscle progenitor cells [20,21].”
BackgroundHoriguchi, N., Lafdil, F., Miller, A. M., Park, O., Wang, H., Rajesh, M., Mukhopadhyay, P., Fu, X. Y., Pacher, P., & Gao, B. (2010) · Hepatology · doi:10.1002/hep.23532 · Cited by 65
“produced, interleukin-6 (IL-6) has been shown to be a hepatoprotective cytokine in this model(15) as well as in several other liver injury models, including ischemia/ reperfusion, partial hepatectomy, alcoholic and nonalcoholic fatty liver, and concanavalin A (Con A)– induced T cell hepatitis.(16-20) Additionally, the…”
BackgroundJAK-STAT signaling in hepatic fibrosis
Mair, M. (2011) · Frontiers in bioscience · doi:10.2741/3886 · Cited by 64
“IL-6-deficient mice are more susceptible to liver injury induced by ethanol (60), Con A (46, 61) acetaminophen (62, 63) and bile acids (64), suggesting that IL-6 has protective functions (65, 66).”
BackgroundRole of biomaterials, therapeutic molecules and cells for hepatic tissue engineering
Vasanthan, K. S., Subramanian, A., Krishnan, U. M., & Sethuraman, S. (2012) · Biotechnology Advances · doi:10.1016/j.biotechadv.2012.01.004 · Cited by 64
Echevarria, F. D., Formichella, C., & Sappington, R. M. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00318 · Cited by 53
“Scale bars= 100µm for all images. strongly associated with wound healing and tissue regeneration in other systems (Blindenbacher et al., 2003; Lin et al., 2003; Tiberio et al., 2008; McFarland-Mancini et al., 2010).”
BackgroundPlacenta extract promote liver regeneration in CCl4-injured liver rat model
Jung, J., Lee, H., Lee, J. M., Na, K.-H., Hwang, S. G., & Kim, G. J. (2011) · International Immunopharmacology · doi:10.1016/j.intimp.2011.02.012 · Cited by 61
Longo, C. R., Patel, V. I., Shrikhande, G. V., Scali, S. T., Csizmadia, E., Daniel, S., Sun, D. W., Grey, S. T., Arvelo, M. B., & Ferran, C. (2005) · Hepatology · doi:10.1002/hep.20741 · Cited by 60
Annexin Animal Models—From Fundamental Principles to Translational Research
Grewal, T., Rentero, C., Enrich, C., Wahba, M., Raabe, C. A., & Rescher, U. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22073439 · Cited by 58
Cheng, L., Wang, J., Li, X., Xing, Q. R., Du, P., Su, L., & Wang, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017631 · Cited by 55
“IL-6 could promote liver regeneration [19–21] and protects hepatocyte death induced by concanavalin A (ConA), anti-Fas, alcohol, acetaminophen, or carbon tetrachloride mediated hepatic damage through the signal transducer and activator of transcription 3 (STAT3) pathway after engaging the heterodi-”
BackgroundSerum Levels of Interleukin-6 and Its Soluble Receptors in Patients with Hepatitis C Virus Infection
Migita, K., Abiru, S., Maeda, Y., Daikoku, M., Ohata, K., Nakamura, M., Komori, A., Yano, K., Yatsuhashi, H., Eguchi, K., et al. (2006) · Human Immunology · doi:10.1016/j.humimm.2006.02.025 · Cited by 51
Molecular dissection of gp130-dependent pathways in hepatocytes during liver regeneration
Dierssen, U., Beraza, N., Lutz, H. H., Liedtke, C., Ernst, M., Wasmuth, H. E., & Trautwein, C. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m705483200 · Cited by 48
Amemiya, H., Kono, H., & Fujii, H. (2009) · Journal of Surgical Research · doi:10.1016/j.jss.2009.08.008 · Cited by 47
“Tumor necrosis factor (TNF)-a and interleukin (IL)-6 have been implicated as important factors for initiating the regenerative responses after PH, a conclusion derived from studies with anti-TNF-a antibodies and mice lacking TNFR-1 or IL-6 [1, 2].”
BackgroundAhmed, Y. A., Fu, Y., Rodrigues, R. M., He, Y., Guan, Y., Guillot, A., Ren, R., Feng, D., Hidalgo, J., Ju, C., et al. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-021-00731-7 · Cited by 46
IL-6 Promotes compensatory liver regeneration in cirrhotic rat after partial hepatectomy
Tiberio, G. A. M., Tiberio, L., Benetti, A., Cervi, E., Montani, N., Dréano, M., Garotta, G., Cerea, K., Steimberg, N., Pandolfo, G. P., et al. (2008) · Cytokine · doi:10.1016/j.cyto.2008.03.012 · Cited by 45
“Among several cytokines and growth factors involved in liver regeneration, IL-6 has been shown to play a major role [3,4].”
BackgroundRad50 Is Dispensable for the Maintenance and Viability of Postmitotic Tissues
Adelman, C. A., De, S., & Petrini, J. H. J. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01525-08 · Cited by 45
Vaquero, J., Campbell, J. S., Haque, J. A., McMahon, R. S., Riehle, K. J., Bauer, R. L., & Fausto, N. (2011) · Hepatology · doi:10.1002/hep.24420 · Cited by 45
“KO – – 52 (10-133) – 51 (40-59) 1 (0-10) 83 (73-85)”
MicroRNAs in Liver Regeneration
Chen, X., Zhao, Y., Wang, F., Bei, Y., Xiao, J., & Yang, C. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000430381 · Cited by 44
Tachibana, S., Zhang, X., Ito, K., Ota, Y., Cameron, A. M., Williams, G. M., & Sun, Z. (2014) · Cell & Bioscience · doi:10.1186/2045-3701-4-6 · Cited by 43
“While IL-6 has been shown to be vital for liver regeneration [6,13,14], the specific mechanisms and factors involved remain incompletely defined.”
BackgroundA Critical Role for Matrix Metalloproteinases in Liver Regeneration
Alwayn, I. P. J., Verbesey, J. E., Kim, S., Roy, R., Arsenault, D. A., Greene, A. K., Novak, K., Laforme, A., Lee, S., Moses, M. A., et al. (2008) · Journal of Surgical Research · doi:10.1016/j.jss.2007.04.002 · Cited by 43
“tion factor that initiates hepatocyte replication [7].”
Canna, S., Frankovich, J., Higgins, G. C., Narkewicz, M. R., Nash, S., Hollister, J. R., Soep, J. B., & Dragone, L. L. (2009) · Pediatric Rheumatology · doi:10.1186/1546-0096-7-21 · Cited by 43
“In contrast, signaling through TNFα and IL-6 receptors on hepatocytes can elicit signals that promote liver regeneration [17,18].”
BackgroundNechemia-Arbely, Y., Shriki, A., Denz, U., Drucker, C., Scheller, J., Raub, J., Pappo, O., Rose-John, S., Galun, E., & Axelrod, J. H. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2010.08.017 · Cited by 42
“IL-6 expression, which dramatically increases shortly following PH [4], appears to be critical to the early onset of liver regeneration and has been shown to mediate both pro-mitotic and pro-survival activities within the regenerative process [5–8], although, the specific role of IL-6 in the mitotic response remains c…”
BackgroundWang, H., Park, O., Lafdil, F., Shen, K., Horiguchi, N., Yin, S., Fu, X.-Y., Kunos, G., & Gao, B. (2009) · Hepatology · doi:10.1002/hep.23430 · Cited by 41
Álvarez-Guaita, A., Blanco‐Muñoz, P., Meneses‐Salas, E., Wahba, M., Pollock, A. H., Jose, J., Casado, M., Bosch, M., Artuch, R., Gaus, K., et al. (2020) · Hepatology · doi:10.1002/hep.31232 · Cited by 41
“(2) Intriguinly, whereas the majority of knockout mouse models described to date display a delayed, rather than complete, abrogation of regeneration,(1) the present study identifies AnxA6 as a decisive factor crucial in the posthepatectomy phase, a feature that is documented only for a rare number of genes.(23,28,29)…”
BackgroundLiver regeneration--the best kept secret. A model of tissue injury response.
Cienfuegos, J. A., Rotellar, F., Baixauli, J., Martínez-Regueira, F., Pardo, F., & Hernández-Lizoáin, J. L. (2014) · PubMed · Cited by 40
Mechanisms of interleukin-6 protection against ischemia–reperfusion injury in rat liver
Tiberio, L., Tiberio, G. A. M., Bardella, L., Cervi, E., Cerea, K., Dréano, M., Garotta, G., Fra, A., Montani, N., Bravo, A. F., et al. (2006) · Cytokine · doi:10.1016/j.cyto.2006.04.009 · Cited by 40
Shteyer, E., Yaʼacov, A. B., Zolotaryova, L., Sinai, A., Lichtenstein, Y., Pappo, O., Kryukov, O., Elkayam, T., Cohen, S., & Ilan, Y. (2014) · Acta Biomaterialia · doi:10.1016/j.actbio.2014.02.047 · Cited by 39
Muriel, P. (2007) · Wiley eBooks · doi:10.1002/9780470516751.ch14 · Cited by 39
Schisandrol B promotes liver regeneration after partial hepatectomy in mice
Li, X., Sun, J., Fan, X., Guan, L., Li, D., Zhou, Y., Zeng, X., Chen, Y., Zhang, H., Xu, L., et al. (2017) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2017.10.044 · Cited by 35
Protective Effects of Early CD4+ T Cell Reduction in Hepatic Ischemia/Reperfusion Injury
Martin, M., Mory, C., Prescher, A., Wittekind, C., Fiedler, M., & Uhlmann, D. (2009) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-009-1104-3 · Cited by 36
Interleukin-18: a pro-inflammatory cytokine that plays an important role in acute pancreatitis
Yuan, B., Zhu, R.-M., Braddock, M., et al. (2007) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728222.11.10.1261 · Cited by 35
“More studies demonstrated that high IL-18 levels in the liver of patients with fulminant hepatic failure [81,82] and overexpression of IL-18 may cause substantial liver injury in vivo [72] .”
BackgroundResolving the Role of Il–6 in Liver Regeneration
Zimmers, T. A., Pierce, R. H., McKillop, I. H., & Koniaris, L. G. (2003) · Hepatology · doi:10.1016/j.hep.2003.09.021 · Cited by 35
Chae, M. S., Moon, K. U., Chung, H. S., Park, C. S., Lee, J., Choi, J. H., & Hong, S. H. (2018) · PLoS ONE · doi:10.1371/journal.pone.0195262 · Cited by 34
Graf, D., Kohlmann, C., Haselow, K., Gehrmann, T., Bode, J. G., & Häussinger, D. (2006) · Hepatology · doi:10.1002/hep.21368 · Cited by 32
Nakamura, T., Ueno, T., Sakamoto, M., Sakata, R., Torimura, T., Hashimoto, O., Ueno, H., & Sata, M. (2004) · Journal of Hepatology · doi:10.1016/j.jhep.2004.08.015 · Cited by 33
“This effect seems to be in agreement with previous results reported by other investigators; IL-6 has been described as an acute-phase inducer in the liver and its induction time is several hours after a variety of liver-injury, such as toxic damage, partial hepatectomy, and ischemic liver injury [5,56–58].”
BackgroundResultJin, C., Samuelson, L., Cui, C.-B., Sun, Y.-Z., & Gerber, D. A. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.05.094 · Cited by 33
“Previous studies showed multiple signaling pathways, including EGF [4,19], IL-6 [20,21] and Wnt [22–24], have vital roles in liver regeneration and oval cell activation after liver injury.”
BackgroundRen, X., Hu, B., & Colletti, L. M. (2008) · Surgery · doi:10.1016/j.surg.2008.03.021 · Cited by 31
Gomez, D. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i5.657 · Cited by 32
Uhlmann, D., Gaebel, G., Armann, B., Ludwig, S., Hess, J., Pietsch, U., Fiedler, M., Tannapfel, A., Hauss, J., & Witzigmann, H. (2005) · Surgery · doi:10.1016/j.surg.2005.07.006 · Cited by 31
Regulation of mammalian cell cycle progression in the regenerating liver
Chauhan, A., Lorenzen, S., Herzel, H., & Bernard, S. (2011) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2011.05.026 · Cited by 30
“Our aim is to address one cycle of division during liver regeneration triggered by a decaying damage (Hayashi et al., 2003; Blindenbacher et al., 2003).”
BackgroundZeini, M., Hortelano, S., Través, P. G., Gómez-Valadés, A. G., Pujol, A., Perales, J. C., Bartrons, R., & Boscá, L. (2005) · The FASEB Journal · doi:10.1096/fj.04-3233fje · Cited by 30
“factors, such as NF-κB (10) and Stat-3 (11), although their exact contribution has been subject of debate (8, 12).”
BackgroundHuard, J., Mueller, S., Gilles, E. D., Klingmüller, U., & Klamt, S. (2012) · The FEBS Journal · doi:10.1111/j.1742-4658.2012.08572.x · Cited by 29
Genomic dissection of the cytokine-controlled STAT5 signaling network in liver
Hosui, A., & Hennighausen, L. G. (2008) · Physiological Genomics · doi:10.1152/physiolgenomics.00048.2008 · Cited by 29
Anatomy, pathophysiology and basic mechanisms of disease
Crawford, J. M., & Burt, A. D. (2011) · Elsevier eBooks · doi:10.1016/b978-0-7020-3398-8.00001-5 · Cited by 32
Reusswig, F., Fazel Modares, N., Brechtenkamp, M., Wienands, L., Krüger, I., Behnke, K., Lee‐Sundlov, M. M., Herebian, D., Scheller, J., Hoffmeister, K. M., et al. (2021) · Hepatology · doi:10.1002/hep.31698 · Cited by 28
“IL- 6 is critically involved in hepatocyte proliferation and liver regeneration after PHx.(44,45) To investigate whether IL- 6 is able to stimulate thrombopoiesis, we treated mice with recombinant hIL6.”
Gock, M. C., Eipel, C., Linnebacher, M., et al. (2011) · Microvascular Research · doi:10.1016/j.mvr.2011.03.005 · Cited by 28
Blanc, V., Sessa, K. J., Kennedy, S., Luo, J., & Davidson, N. O. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.115147 · Cited by 28
Lanton, T., Shriki, A., Nechemia‐Arbely, Y., Abramovitch, R., Levkovitch‐Siany, O., Adar, R., Rosenberg, N., Paldor, M., Goldenberg, D., Sonnenblick, A., et al. (2016) · Hepatology · doi:10.1002/hep.29004 · Cited by 28
“0054 by Fisher’s exact test), perhaps reflecting the sensitivity of IL6 knockout mice to liver resection.((18,21,22)) In contrast, we found that a single administration of an antiIL6 mAb (100 lg, intravenously) to Mdr2 (FVB/ NJ) mice, the strain used in our previous study,((16)) at the time of resection did not dimini…”
BackgroundStructure, Function, and Responses to Injury
Crawford, J. M., Bioulac‐Sage, P., & Hytiroglou, P. (2017) · Elsevier eBooks · doi:10.1016/b978-0-7020-6697-9.00001-7 · Cited by 28
Liver Regeneration: A Link to Inflammation through Complement
DeAngelis, R. A., Markiewski, M. M., & Lambris, J. D. (2007) · Springer eBooks · doi:10.1007/0-387-34134-x_2 · Cited by 26
Toll-like receptor 5-mediated signaling enhances liver regeneration in mice
Zhang, W., Wang, L., Sun, X., Liu, X., Xiao, Y., Zhang, J., Wang, T., Chen, H., Zhan, Y., Yu, M., et al. (2021) · Military Medical Research · doi:10.1186/s40779-021-00309-4 · Cited by 27
“Upon the stimulation of these proin ammatory cytokines, normally quiescent hepatocytes regain proliferative competence and become responsive to hepatic growth factors [4,5,6].”
BackgroundBoubaddi, M., Marichez, A., Adam, J., Lapuyade, B., Debordeaux, F., Tlili, G., Chiche, L., & Laurent, C. (2024) · Annals of Surgical Oncology · doi:10.1245/s10434-024-16108-9 · Cited by 26
“24 28 This induction phase ceases as hepatocytes enter the cell cycle (Fig.”
Pathophysiological Changes During Ischemia-reperfusion Injury in Rodent Hepatic Steatosis
Neri, A.-A., Dontas, I. A., Iliopoulos, D., & Karatzas, T. (2020) · In Vivo · doi:10.21873/invivo.11863 · Cited by 26
Wong, S., Ting, Y., Yong, Y.-K., Tan, H.-Y., Barathan, M., Riazalhosseini, B., Bee, C. J., Tee, K. K., Larsson, M., Velu, V., et al. (2021) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2021.1876245 · Cited by 28
Kono, H., Fujii, H., Suzuki‐Inoue, K., Inoue, O., Furuya, S., Hirayama, K., Akazawa, Y., Nakata, Y., Sun, C., Tsukiji, N., et al. (2017) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.13672 · Cited by 24
“Activation of intracellular signaling cascades after hepatectomy The proliferation of hepatocytes requires two sequential phases: a priming phase and progression phase [2,4,5].”
BackgroundInfluential
Metadata
- Authors
- Blindenbacher, A., Wang, X., Langer, I., Savino, R., Terracciano, L., & Heim, M. H.
- Affiliations
- University Hospital of Basel (CH)
- Magna Graecia University (IT)
- Corresponding author
- Heim, Markus H.
- Venue
- Hepatology
- Published
- 2003-09
- Volume
- 38
- Issue
- 3
- Pages
- 674-682
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2048242463
- Semantic Scholar
- 78c7f4e4325ae9116023347a3571832ba7e4a329
- Cited by
- 202
- References
- 33
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 9 · 2020: 11 · 2019: 6 · 2018: 6 · 2017: 13 · 2016: 5 · 2015: 7 · 2014: 11 · 2013: 5 · 2012: 12
- FWCI
- 6.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Keywords
- interleukin-6, partial hepatectomy, postoperative survival, acute phase response, liver regeneration, IL-6 knockout mice, homeostasis
- MeSH terms
- Acute-Phase Proteins, Animals, Cell Cycle, DNA-Binding Proteins, Hepatectomy, Injections, Subcutaneous, Liver, Liver Regeneration, Time Factors, Trans-Activators, Interleukin-6, Survival Rate, Mice, Knockout, STAT3 Transcription Factor, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-23, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-23 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
