The DOI matches its Crossref record; 42 of the 43 references it cites were found in a registry or an index; none of the 16 sources its claims cite is checked for support yet.
Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia/reperfusion injury in the rat.
Open accessAbstract
Cytokines are recognized as critical early mediators of organ injury. We attempted to determine whether or not severe hepatic ischemia/reperfusion injury results in tumor necrosis factor-alpha (TNF-alpha) release with subsequent local and systemic tissue injury. After 90 min of lobar hepatic ischemia, TNF was measurable during the reperfusion period in the plasma of all 14 experimental animals, with levels peaking between 9 and 352 pg/ml. Endotoxin was undetectable in the plasma of these animals. Pulmonary injury, as evidenced by a neutrophilic infiltrate, edema and intra-alveolar hemorrhage developed after hepatic reperfusion. The neutrophilic infiltrate was quantitated using a myeloperoxidase (MPO) assay; this demonstrated a significant increase in MPO after only 1 h of reperfusion. Anti-TNF antiserum pretreatment significantly reduced the pulmonary MPO after hepatic reperfusion. After a 12-h reperfusion period, there was histologic evidence of intra-alveolar hemorrhage and pulmonary edema. Morphometric assessment showed that pretreatment with anti-TNF antiserum was able to completely inhibit the development of pulmonary edema. Liver injury was quantitated by measuring serum glutamic pyruvic transaminase which showed peaks at 3 and 24 h. Anti-TNF antiserum pretreatment was able to significantly reduce both of these peak elevations. These data show that hepatic ischemia/reperfusion results in TNF production, and that this TNF is intimately associated with pulmonary and hepatic injury.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
In a rat model of 90-minute lobar hepatic ischemia/reperfusion, TNF became measurable in plasma in all 14 experimental animals and was associated with subsequent pulmonary and hepatic injury. Pretreatment with anti-TNF antiserum reduced pulmonary neutrophil sequestration, abolished pulmonary edema, and lowered serum SGPT elevations after reperfusion.
Key findings
- After hepatic ischemia/reperfusion, TNF was measurable in plasma of all 14 experimental animals, with a mean peak level of 69.4±30.3 pg/ml and a range of 9–352 pg/ml; TNF was undetectable in sham-operated controls, and endotoxin was undetectable (<5 pg/ml).
- Pulmonary neutrophil sequestration, measured by MPO, peaked after 1 h of reperfusion at 0.653±0.089 U versus 0.213±0.034 U in sham animals (P<0.005). Anti-TNF antiserum reduced MPO to 0.458±0.057 U compared with 0.701±0.040 U in control-serum animals (P<0.005), though it did not return values to sham baseline.
- After 12 h of reperfusion, control-serum animals had 20±4 flooded alveoli/high-power field, whereas anti-TNF antiserum-treated animals had 0±0 (P<0.05 by Wilcoxon rank-sum test).
- Serum SGPT peaked at 3 and 24 h after reperfusion; anti-TNF antiserum significantly reduced both peak elevations (P<0.05 at 3 h and P<0.005 at 24 h versus untreated and control-serum groups). Twenty-four-hour survival was 67% in untreated animals, 92% with anti-TNF antiserum, and 60% with control serum, but the differences were not statistically significant.
Methods
- Adult male pathogen-free Sprague-Dawley rats (200–300 g) underwent 90 min of lobar hepatic ischemia using a Heifitz clip, with sham-operated controls treated identically except for vascular occlusion.
- Plasma TNF activity was measured with a WEHI 164 subclone 13 bioassay; positive samples were confirmed by neutralization with polyclonal rabbit anti-murine TNF antiserum. Endotoxin was measured by a perchloric acid-modified chromogenic limulus assay.
- Organ injury was assessed by pulmonary MPO assay, blinded histologic morphometry of edema-filled alveoli, and serum SGPT. Anti-TNF effects were tested by pretreating rats with polyclonal rabbit anti-murine TNF antiserum versus control rabbit serum. Statistical comparisons used Student Newman-Keuls or Wilcoxon rank-sum tests when data were not normally distributed.
Limitations
- The paper states that 24-h survival differences were not statistically significant, most likely because of relatively small group sizes.
- The paper states that further studies are needed to document the degree to which the observed pulmonary pathology is neutrophil dependent.
- The paper states that the mechanism of TNF induction after hepatic ischemia/reperfusion is not completely clear; the text infers Kupffer cell production/leakage but does not directly establish the cellular source.
- Evident from the text: anti-TNF antiserum did not prevent the transient hypotension after revascularization, so the protective effects observed were not attributable to hemodynamic stabilization.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
0 of 16 cited sources checked · 0 supported · 0 flagged
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 90 min of lobar hepatic ischemia, TNF was measurable during the reperfusion period in the plasma of all 14 experimental animals, with levels peaking between 9 and 352 pg/ml.”
- Also stated in: § Results · plain
“TNF was measurable in the plasma of all 14 experimental animals”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Results · 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
“Endotoxin was undetectable in the plasma of these animals.”
- Also stated in: § Results · plain
“In addition, endotoxin was unde- tectable (< 5 pg/ml).”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Results · 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
“TNF was un- detectable at any time point in the three sham-operated con- trol animals”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Results
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
“The neutrophilic infiltrate was quantitated using a myeloperoxidase (MPO) assay; this demonstrated a significant increase in MPO after only 1 h of reperfusion.”
- Also stated in: § Results · plain
“1 h postrevascularization, mean pulmonary MPO was 0.653±0.089U as compared with 0.213±0.034U for sham-operated animals (P < 0.005; Fig. 3.).”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Results · 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
“Pulmonary injury, as evidenced by a neutrophilic infiltrate, edema and intra-alveolar hemorrhage developed after hepatic reperfusion.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Abstract
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
“and that a picture of pulmonary neutrophil sequestration and hemorrhagic edema develops.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Discussion
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
“of 12 animals treated with anti-TNF antiserum before the induction of hepatic ischemia, 11 animals survived for 24 h, giving a 24-h survival of 92%.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > .)
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
“For animals undergoing hepatic ischemia and reperfusion alone, the mean minimum systolic blood was significantly different from sham-operated an- imals (P < 0.005).”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Results
Strength:plain· 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
“Of 24 animals undergoing 90 min of lobar hepatic ischemia and 24 h of reperfusion, eight animals ex- pired before 24 h, resulting in a 24-h survival of 67%.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > .)
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
“This was not the result of protection from a hypotensive effect, since the anti-TNF and control serum groups showed the same degree of transient hypotension after clamp release.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 17
- The quote only partly states this claim. 3
- Probably not a substantial claim. 7
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 mean peak TNF level was 69.4±30.3pg/ml with a range of 9-352 pg/ml.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Results
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
“Thus, anti-TNF treatment blunted the increase in pulmonary MPO but did not reduce the MPO level to that observed in sham-operated controls.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Results
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
“MPO levels were maximal after 1 h of reperfusion and gradually decreased over the next 11 h.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Results
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ 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
“24 h survival in animals treated with control serum was similar to that seen in the untreated experimental group with 6 of 10 animals surviving for 24 h.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > .)
Strength:plain· not yet calibratedn = 10Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ 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 anti-TNF-treated rats illustrate essentially normal histology.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
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
“Anti-TNF antiserum pretreatment was able to significantly reduce both of these peak elevations.”
- Also stated in: § Results · plain
“SGPT levels were significantly decreased both 3 and 24 h postrevascularization in the animals treated with anti-TNF antiserum as compared to untreated experimental animals and animals treated with control serum (P < 0.05 after 3 h of reperfusion and”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Results · 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
“Statistical significance was not achieved between any of the groups, most likely due to the relatively small numbers in the groups.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > .)
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
“After 3 h of hepatic reperfusion, there was a significant decrease in SGPT in animals pretreated with anti-TNF antiserum as compared with both the untreated ex- perimental animals and the control serum-treated animals.”
- Also stated in: § Discussion · hedged
“Animals treated with anti-TNF antiserum showed a significant reduction in a hepatocyte-specific enzyme (SGPT) after hepatic ischemia/reperfusion in comparison to controls treated with control serum”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
- Also stated in: § Discussion · hedged
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
“Anti-TNF antiserum pretreatment significantly reduced the pulmonary MPO after hepatic reperfusion.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesThe quote only partly states this claim.
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 operated rats show intra-alveolar hemorrhage and some edema fluid.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Recent clinical data have shown that impaired hepatic function greatly influences severity and impedes reso- lution of ARDS (4).”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Introduction
What the sources say
- Not checked yetcites [4]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It 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
“Since the pulmonary circulation represents the first vascu- lar bed into which these cytokines are delivered, the pulmonary parenchyma would be likely to manifest the toxic effects of these cytokines.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Introduction
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: The pulmonary circulation is the first vascular bed into which cytokines from injured liver are delivered.
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 lower limit of endotoxin detection in this assay is 5 pg/ml.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Methods
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
“The TNF release also did not appear directly related to the hypotensive effect produced by the I/R process, since anti-TNF antiserum treatment blocked the observed pathology, but did not alter the hypotension following clamp release.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Discussion
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“primary nonfunction of the graft after liver transplantation is also associated with the rapid development ofpulmonary insufficiency (5).”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Introduction
What the sources say
- Not checked yetcites [5]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
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 pulmonary pathology appears to be a consequence of TNF, since pretreatment with neutralizing anti-TNF anti- serum blunted the neutrophilic infiltrate (as measured by MPO) and completely abolished both the diffuse edema and patchy hemorrhage.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Discussion
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
“Slides were examined in a blinded manner.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Myeloperoxidase (MPO) assay. Pulmonary neutrophil sequestra- tion was quantitated with the MPO assay (I14).
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.
In the paper
“Previous in vitro studies have docu- mented the ability of Kupffer cells to produce TNF (28).”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Discussion
What the sources say
- Not checked yetcites [28]
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.
In the paper
“This antiserum neutralizes both natural and recombinant TNF, cross-reacts with rat TNF and has no cross-reactivity with interleukin 1.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Methods
What the sources say
- Not checked yetcites 1 1, 12
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Previous studies have documented a deleterious effect of TNF on the hepatocyte where infused rTNF results in focal hepatic necrosis, as does LPS infusion, and the latter finding could be blocked with anti-TNF antiserum (13).”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Discussion
What the sources say
- Not checked yetcites [13]
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.
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
“However, our model was specifically chosen to avoid such vascular con- gestion, involving only lobar vascular occlusion with unim- peded portal flow to the right lobe.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Discussion
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The three caudal lobes retain an intact portal inflow and venous out- flow, preventing intestinal venous congestion and possible leakage of bacteria or bacterial products into the circulation.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Methods
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“These data confirm our earlier study which used an intravenous ra- dioactive tracer to document protein leakage into the lungs (9).”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Results
What the sources say
- Not checked yetcites [9]
Strength:plain· not yet calibratedn = 5Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“By utilizing a rat model of lobar, rather than total, hepatic ischemia, a severe ischemic insult was produced without in- ducing mesenteric venous hypertension (8).”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Methods
What the sources say
- Not checked yetcites [8]
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
“and that TNF has both local deleterious effects on the hepatocyte and extensive damaging effects on pulmonary integrity.”
§ Role of Tumor Necrosis Factor-a in the Pathophysiologic Alterations after Hepatic Ischemia/Reperfusion Injury in the Rat > Discussion
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
The paper relies on this without support.
TNF is produced primarily by cells of the monocyte/macrophage lineage.
“TNF is produced primarily by cells of the monocyte/macrophage lineage”
The paper relies on this without support.
The liver Kupffer cell mass is the largest fixed macrophage population in the body.
“the liver Kupffer cell mass is the largest fixed macrophage population in the body.”
The paper relies on this without support.
The pulmonary circulation is the first vascular bed into which cytokines from injured liver are delivered.
“the pulmonary circulation represents the first vascu- lar bed into which these cytokines are delivered”
The paper relies on this without support.
The anti-TNF antiserum used in these experiments neutralizes TNF in vivo and does not have other relevant biological activities that could account for the observed protection.
“pretreatment with neutralizing anti-TNF anti- serum blunted the neutrophilic infiltrate”
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?
In the citing paper
“Reperfusion of ischemic tissues stimulates cytokine overproduction (e.g., TNF, IL-1, HMGB1), which contributes to the pathogenesis of resulting tissue damage (42)(43)(44).”
From Physiology and immunology of the cholinergic antiinflammatory pathway (2007) · cites this paper as [43]
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-injury claim cites the Limulus-assay reference
MinorThe discussion cites reference 13 for prior findings about TNF, LPS, and hepatic necrosis, but reference 13 describes a method for the Limulus test rather than those findings.
“Previous studies have documented a deleterious effect of TNF on the hepatocyte where infused rTNF results in focal hepatic necrosis, as does LPS infusion, and the latter finding could be blocked with anti-TNF antiserum (13).”
“13. Obayashi, T. 1984. Addition of perchloric acid to blood sam- ples for colorimetric limulus, test using chromogenic substrate: com- parison with conventional procedures and clinical applications. J. Lab. Clin. Med. 104:321-330.”
Allograft-rejection citation points to a parasitic-infection paper
MinorThe text cites reference 24 for TNF in renal allograft rejection, but reference 24 is titled as a study of parasitic infections. The renal allograft rejection paper appears as reference 25.
“renal allograft rejection (24)”
“24. Scuderi, P., K. E. Sterling, K. S. Lam, P. R. Finley, K. J. Ryan, C. G. Ray, E. Peterson, D. J. Slyman, and S. E. Salmon. 1986. Raised serum levels of tumor necrosis factor in parasitic infections. Lancet. 1:1364-1365.”
Citations
Cites
Shock and Tissue Injury Induced by Recombinant Human Cachectin
Tracey, K. J., Beutler, B., Lowry, S. F., Merryweather, J., Wolpe, S., Milsark, I. W., Hariri, R. J., Fahey, T. J., Zentella, A., Albert, J. D., et al. (1986) · Science · doi:10.1126/science.3764421 · Cited by 2,549
Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia
Tracey, K. J., Fong, Y., Hesse, D. G., Manogue, K. R., Lee, A. T., Kuo, G. C., Lowry, S. F., & Cerami, A. (1987) · Nature · doi:10.1038/330662a0 · Cited by 2,448
Detection of circulating tumor necrosis factor after endotoxin administration
Michie, H. R., Manogue, K. R., Spriggs, D. R., Revhaug, A., O'Dwyer, S., Dinarello, C. A., Cerami, A., Wolff, S. M., & Wilmore, D. W. (1988) · New England Journal of Medicine · doi:10.1056/nejm198806093182301 · Cited by 1,677
Espevik, T., & Nissen-Meyer, J. (1986) · Journal of Immunological Methods · doi:10.1016/0022-1759(86)90322-4 · Cited by 1,256
Waage, A., Halstensen, A. I., & Espevik, T. (1987) · The Lancet · doi:10.1016/s0140-6736(87)91728-4 · Cited by 1,085
Bevilacqua, M. P., Pober, J. S., Majeau, G. R., Fiers, W. C., Cotran, R. S., & Gimbrone, M. A. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.12.4533 · Cited by 1,059
Gamble, J. R., Harlan, J. M., Klebanoff, S. J., & Vadas, M. A. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.24.8667 · Cited by 1,031
Shalaby, M. R., Aggarwal, B. B., Rinderknecht, E., Svedersky, L. P., Finkle, B. S., & Palladino, M. A. (1985) · The Journal of Immunology · doi:10.4049/jimmunol.135.3.2069 · Cited by 916
Tumor Necrosis Factor and Disease Severity in Children with Falciparum Malaria
Grau, G. E., Taylor, T. E., Molyneux, M. E., Wirima, J. J., VASSALLI, P., Hommel, M., & Lambert, P. (1989) · New England Journal of Medicine · doi:10.1056/nejm198906153202404 · Cited by 839
Stimulation of neutrophils by tumor necrosis factor.
Klebanoff, S. J., Vadas, M. A., Harlan, J. M., Sparks, L., Gamble, J. R., Agosti, J. M., & Waltersdorph, A. M. (1986) · The Journal of Immunology · doi:10.4049/jimmunol.136.11.4220 · Cited by 832
Flagged first, then by citations
1 of the 43 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Glantz, S. A. 1987. Primer of Biostatistics. 2nd edition.
- Bevilacqua, M. P., J. S. Pober, G. R. Majeau, W. Fiers, R. S. Cotran, and M. A. Gimbrone. 1986. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endo- thelium. Proc. Natl. Acad. Sci. USA. 83:4533-4537.
Cited by
Sorted by citations
Items 801–821 of 821
Wanner, G. A., Erte, W., Mtiller, P., et al. (1992)
Tuna, A. T., Demirel, C. B., Ünal, Y., et al. (2013) · TURKISH JOURNAL OF MEDICAL SCIENCES · doi:10.3906/sag-1205-47
Cytokines in liver, biliary, and pancreatic disease
Maggi, J. C., & Miller, G. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-34062-5.00011-x
HepatoprotektiveWirkungen des Hämoxygenase-Stoffwechsels: Der Einfluss von Anästhetika
Bauer, I., Halverscheid, L., & Pannen, B. H. J. (2021) · De Gruyter eBooks · doi:10.1515/9783110718836-011
Identifying Novel Therapies to Reduce Injury following Ischemia Reperfusion in Kidney
Reid, S. (2021) · TSpace (University of Toronto)
Chen, Z., Lin, R., Zhuo, H., et al. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06879-9
Methods to Reduce Liver Ischemia/Reperfusion Injury
Björnsson, B. (2014) · Linköping University medical dissertations · doi:10.3384/diss.diva-110318
“IL-6 moderates the inflammatory response and reduces TNF-α expression as well as IRI (137-139).”
BackgroundAcute liver failure — mechanisms of liver cell destruction
Trautwein, C., Liedtke, C., Streetz, K. L., Luedde, T., & Klein, C. (2007) · Springer eBooks · doi:10.1007/1-4020-4144-6_25
Lüdde, T., & Trautwein, C. (2005) · Springer eBooks · doi:10.1007/3-540-27194-5_29
Deng, M. C.-H. K. (1997) · Steinkopff eBooks · doi:10.1007/978-3-642-48012-6_5
Carlet, J. M., Tamion, F., & Cabie, A. (1996) · Update in intensive care and emergency medicine · doi:10.1007/978-3-642-80224-9_12
Beneficial Effects of Insulin on Ischemia Reperfusion Injury in Human Skeletal Muscle
Gooneratne, T., Homer‐Vanniasinkam, S., & Wijeyaratne, M. (2022) · Vascular Specialist International · doi:10.5758/vsi.220018
Predicting cardiovascular complications after liver transplantation
Gurram, H., Jo, J., & VanWagner, L. B. (2023) · Elsevier eBooks · doi:10.1016/b978-0-12-817394-7.00002-4 · Cited by 1
Villabona-Rueda, A., Wang, D., & D’Alessio, F. R. (2023) · doi:10.3791/63925-v
Mecanismes de senyalització intracel·lulars en isquèmia/reperfusió hepàtica
Durán, L. L. (2009) · TDX (Tesis Doctorals en Xarxa)
Impact of Donor Age and Prolonged Warm Ischemia in Normothermic Machine Perfusion of Rat Livers
Pietsch, A. M., Boerger, L., Padoan, L., et al. (2026) · Tissue Engineering Part A · doi:10.1177/19373341261419492
SETDB1 in Macrophage Protects the Liver from IRI by Inhibiting the P2RX7-Mediated Pyroptosis Pathway
Song, L., Bai, Y., Sun, L., Yi, W., Lan, P., Liu, J., & Chen, S. (2026) · Antioxidants and Redox Signaling · doi:10.1177/15230864261443838
“…of pro-in fl ammatory cytokines in the injured area, including tumor necrosis factor-alpha (TNF-a ), interleukin-1beta (IL-1 b ), interleukin-6 (IL-6), reactive oxygen species (ROS), nitric oxide (NO), complement proteins, and chemokines (Colletti et al., 1990; Kato et al., 2002; Wang et al., 2021).”
Li, W., Yang, L., Lu, J., Yi, S. L., Cao, L., Lei, K., Sheng, Z., & Liu, Z. (2026) · Regenerative Biomaterials · doi:10.1093/rb/rbag084
“To investigate whether GalNAc-MM@PLGA/Mel could trigger an anti-inflammatory activity in vivo , we measured inflammatory factors TNF-α [49] in NAFLD using immunofluorescence staining.”
Blackwell, T. S., Debelak, J. P., Venkatakrishnan, A., Schot, D. J., Harley, D. H., Pinson, C. W., Williams, P., Washington, K., Christman, J. W., & Chapman, W. C. (1999) · Surgery · doi:10.1016/s0039-6060(99)70093-0
Pulmonary Dysfunction after Remote Ischemia and Reperfusion
Groeneveld, A. B. J., & Raijmakers, P. G. H. M. (1995) · Yearbook of intensive care and emergency medicine · doi:10.1007/978-3-642-79154-3_4
Metadata
- Authors
- Colletti, L. M., Remick, D. G., Burtch, G. D., Kunkel, S. L., Strieter, R. M., & Campbell, D. A.
- Affiliations
- University of Michigan (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1990-06-01
- Volume
- 85
- Issue
- 6
- Pages
- 1936-1943
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC296661
- OpenAlex
- W2099883737
- Semantic Scholar
- ef00ab3fc75d2591f58ef3691dd24619b03cf25e
- Cited by
- 817
- References
- 43
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 5 · 2022: 10 · 2021: 8 · 2020: 5 · 2019: 6 · 2018: 16 · 2017: 12 · 2016: 6 · 2015: 15 · 2014: 12 · 2013: 20 · 2012: 24
- FWCI
- 40.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl031237-32)
- National Heart, Lung, and Blood Institute (HL-35276, HL31237, HL 31963, P01HL031963)
- Topics
- Health Sciences › Medicine › Surgery › Organ Transplantation Techniques and Outcomes
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- TNF-α, hepatic ischemia-reperfusion injury, cytokines, pulmonary edema, intra-alveolar hemorrhage, neutrophil infiltration, myeloperoxidase, liver injury, systemic inflammatory response, endotoxin
- MeSH terms
- Alanine Transaminase, Animals, Hemodynamics, Ischemia, Liver, Liver Diseases, Lung, Peroxidase, Neutrophils, Time Factors, Tumor Necrosis Factor-alpha, Reperfusion Injury, Rats
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 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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
