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Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamic-pituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems
Open accessAbstract
Objective To study in parallel the outflow of the sympathetic nervous system (SNS) and the hypothalamic-pituitary adrenal (HPA) axis tone in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).Methods 32 patients with SLE, 62 with RA, and 65 healthy subjects (HS) were included. To measure the tone of the HPA axis, plasma ACTH and serum cortisol were determined. Serum neuropeptide Y (NPY) was used to evaluate the sympathetic outflow.Results Patients with SLE had increased NPY levels in comparison with HS, irrespective of prior prednisolone treatment (p<0.001). For patients with RA, only those with prednisolone treatment had increased NPY levels in comparison with HS (p = 0.016). Daily prednisolone dose correlated positively with serum NPY in RA (R(Rank) = 0.356, p = 0.039). In contrast, plasma ACTH levels were generally decreased significantly in comparison with HS in SLE with prednisolone, and in RA with/without prednisolone. Similarly, serum cortisol levels were also decreased in SLE with/without prednisolone, and in RA with prednisolone. The NPY/ACTH ratio was increased in SLE and RA, irrespective of prior prednisolone treatment. The NPY/cortisol ratio was increased in SLE with/without prednisolone, and in RA with prednisolone. Twelve weeks' anti-TNF antibody treatment with adalimumab did not decrease NPY levels in RA, irrespective of prednisolone treatment.Conclusions An increased outflow of the SNS was shown and a decreased tone of the HPA axis in patients with SLE and RA. Low levels of cortisol in relation to SNS neurotransmitters may be proinflammatory because cooperative anti-inflammatory coupling of the two endogenous response axes is missing.
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TL;DR
In patients with SLE and RA, serum neuropeptide Y indicated increased sympathetic outflow while ACTH/cortisol indicated reduced hypothalamic-pituitary-adrenal axis tone, producing increased NPY/ACTH and NPY/cortisol ratios. This uncoupling was present with or without prednisolone in SLE and mainly in prednisolone-treated RA, and 12 weeks of adalimumab did not reduce NPY levels.
Key findings
- Patients with SLE had increased NPY levels versus healthy subjects, irrespective of prior prednisolone treatment (p<0.001); in RA, only prednisolone-treated patients had increased NPY versus healthy subjects (p=0.016), and daily prednisolone dose correlated positively with serum NPY in RA (R Rank=0.356, p=0.039).
- Plasma ACTH was decreased versus healthy subjects in SLE with prednisolone and in RA with or without prednisolone; serum cortisol was decreased in SLE with or without prednisolone and in RA with prednisolone.
- The NPY/ACTH ratio was increased in SLE and RA irrespective of prior prednisolone treatment; the NPY/cortisol ratio was increased in SLE with or without prednisolone and in RA with prednisolone.
- Twelve weeks of anti-TNF treatment with adalimumab did not decrease NPY levels in RA, irrespective of prednisolone treatment, and neither NPY/ACTH nor NPY/cortisol ratios changed during treatment.
Methods
- The study included 32 patients with SLE, 62 patients with RA, and 65 healthy subjects; subgroups were matched according to age and sex. Blood was drawn between 08:00 and 10:00, and serum NPY, plasma ACTH, and serum cortisol were measured by immunoassays.
- Some patients with RA (16 with and 16 without parallel prednisolone) received adalimumab 40 mg subcutaneously every other week for 12 weeks plus stable methotrexate; blood was drawn at baseline and at weeks 2, 6, and 12.
- Group medians were compared by Mann-Whitney tests, correlations by Spearman rank analysis, and changes over time by Friedman tests; p<0.05 was significant.
Limitations
- Stated in the paper: norepinephrine was not measured because of expected strong bias from prolonged storage, since norepinephrine is more labile than NPY; the authors also note that NPY may not be the ideal measure in older patients when SNS activity is only increased to a small extent.
- Evident from the text: the main SLE/RA versus healthy-subject comparisons are cross-sectional, so temporal or causal direction cannot be established; prednisolone groups were not randomized, and the adalimumab analysis was a small RA subset (16 with and 16 without prednisolone) with no placebo control described in this paper.
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17 Own result · 5 Not checked yet · 5 Own method · 5 Own interpretation
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
“Daily prednisolone dose correlated positively with serum NPY in RA (R Rank = 0.356, p = 0.039).”
- Also stated in: § DISCUSSION · boosted
“Clearly, the prednisolone dose correlated with NPY serum levels in patients with RA but not in patients with SLE (figs 1C and D).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Abstract
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § DISCUSSION · boosted
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
“For patients with RA, only those with prednisolone treatment had increased NPY levels in comparison with HS (p = 0.016).”
- Also stated in: § DISCUSSION · plain
“In RA, only patients with prior prednisolone had increased NPY serum levels in comparison with healthy subjects (fig 1B).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“Twelve weeks' anti-TNF antibody treatment with adalimumab did not decrease NPY levels in RA, irrespective of prednisolone treatment.”
- Also stated in: § DISCUSSION · plain
“Using the Friedman test statistics, 12 weeks of anti-TNF treatment did not change NPY serum levels, irrespective of prednisolone treatment (fig 4).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- 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
“Patients with SLE had increased NPY levels in comparison with HS, irrespective of prior prednisolone treatment (p,0.001).”
- Also stated in: § DISCUSSION · boosted
“Figure 1 demonstrates higher NPY serum levels in patients with SLE than in HS, irrespective of prednisolone treatment (fig 1A).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Abstract
boostedcorrelationaln = 32 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § DISCUSSION · boosted
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 NPY/cortisol ratio was increased in SLE with/without prednisolone, and in RA with prednisolone.”
- Also stated in: § Relation of NPY serum levels and HPA axis hormones · plain
“The ratio of NPY/cortisol was increased in both SLE patient groups, irrespective of prednisolone treatment (fig 3C).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Abstract
plaincorrelationaln = 32- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Relation of NPY serum levels and HPA axis hormones · 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 patients with RA, prednisolone treatment increased this particular ratio (fig 2D).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Relation of NPY serum levels and HPA axis hormones
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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 NPY/ACTH ratio was increased in SLE and RA, irrespective of prior prednisolone treatment.”
- Also stated in: § Relation of NPY serum levels and HPA axis hormones · plain
“The ratio of NPY/ACTH was significantly higher in patients with SLE and RA than in healthy controls, irrespective of prior prednisolone treatment (figs 2C and D).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Relation of NPY serum levels and HPA axis hormones · 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
“Similarly, serum cortisol levels were also decreased in SLE with/without prednisolone, and in RA with prednisolone.”
- Also stated in: § Relation of NPY serum levels and HPA axis hormones · plain
“In RA, only those patients with prior prednisolone treatment had decreased cortisol serum levels (fig 3B).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Relation of NPY serum levels and HPA axis hormones · 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 contrast, plasma ACTH levels were generally decreased significantly in comparison with HS in SLE with prednisolone, and in RA with/without prednisolone.”
- Also stated in: § Relation of NPY serum levels and HPA axis hormones · plain
“In addition, patients with RA without prior prednisolone treatment also had decreased ACTH levels in comparison with healthy subjects (fig 2B).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Relation of NPY serum levels and HPA axis hormones · 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
“Similarly, serum cortisol levels were also decreased in SLE with/without prednisolone, and in RA with prednisolone.”
- Also stated in: § Relation of NPY serum levels and HPA axis hormones · boosted
“For cortisol, patients with SLE demonstrated decreased serum levels, irrespective of prior prednisolone treatment (fig 3A).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Abstract
boostedn = 32- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Relation of NPY serum levels and HPA axis hormones · boosted
- Probably not a substantial claim. 8
- It may state two separate claims as one. 8
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
“Plasma NPY levels did not differ between male and female patients with or without prednisolone (data not shown).”
- Also stated in: § Relation of NPY serum levels and HPA axis hormones · plain
“The above-mentioned ratios did not differ between male and female patients with or without prednisolone (data not shown).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > RESULTS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Also stated in: § Relation of NPY serum levels and HPA axis hormones · 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 addition, neither the ratio of serum NPY/plasma ACTH nor the ratio of serum NPY/serum cortisol changed during 12 weeks of anti-TNF treatment (data not shown).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > DISCUSSION
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“None of the patients without prednisolone received glucocorticoids during a period of 6 months before study entry, whereas patients with prednisolone had stable treatment over several weeks before study entry.”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > PATIENTS AND METHODS
plain- Asserted: passes — The authors put it forward as true.
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Probably 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
“In addition, an increased SNS tone would support atherosclerosis in patients with chronic inflammatory diseases.”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > DISCUSSION
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“This permissive effect of cortisol is due to b adrenoceptor up regulation and stabilisation of the cyclic AMP (cAMP)/protein kinase A/ cAMP responsive element binding protein signalling pathway.30”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > D
What the sources say
- Not checked yetcites [30] Schramm, 2000, beta-Adrenergic relaxation of rabbit tracheal smooth muscle: a receptor deficit that improves with corticosteroid administration, J Pharmacol Exp Ther source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The study was approved by the ethics committee of the University Hospital of Regensburg, Germany, and for the adalimumab study, approval was obtained from the ethics committee of L Sacco University Hospital, Italy.”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > PATIENTS AND METHODS
plain- Asserted: passes — The authors put it forward as true.
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Probably 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
“For all assays, intraassay and interassay coefficients of variation were below 10%.”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Laboratory variables
plain- Asserted: passes — The authors put it forward as true.
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Probably 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
“An increased outflow of the SNS was shown and a decreased tone of the HPA axis in patients with SLE and RA.”
- Also stated in: § DISCUSSION · boosted
“Using NPY as a reliable read-out measure of the SNS activity, we were able to demonstrate an increased SNS outflow in relation to the HPA axis tone in all patients with SLE and in patients with RA treated with prednisolone.”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Abstract
boosted- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § DISCUSSION · boosted
None of the sources cited for this claim have been checked yet.
In the paper
“In chronic inflammatory diseases such as systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) the HPA axis alters markedly : (a) secretion of adrenocorticotropic hormone (ACTH) relative to circulating cytokines is inadequate 7 ; (b) patients have inappropriately low sponta- neous and stimulated cortisol secretion in relation to inflammation”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > D
What the sources say
- Not checked yetcites [7] Straub, 2002, Inadequately low serum levels of steroid hormones in relation to IL-6 and TNF in untreated patients with early rheumatoid arthritis and reactive arthritis, Arthritis Rheum source
- Not checked yetcites [8] Gudbjornsson, 1996, Intact adrenocorticotropic hormone secretion but impaired cortisol response in patients with active rheumatoid arthritis. Effect of glucocorticoids, J Rheumatol
- Not checked yetcites [9] Crofford, 1997, Circadian relationships between interleukin (IL)-6 and hypothalamic- pituitary-adrenal axis hormones: failure of IL-6 to cause sustained hypercortisolism in patients with early untreated rheumatoid arthritis, J Clin Endocrinol Metab source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“NPY is an excellent indicator of sympathetic activity, 34 which is more stable and has a significantly longer half life in plasma.35”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > D
What the sources say
- Not checked yetcites [34] Morris, 1986, Increases in plasma neuropeptide Y concentrations during sympathetic activation in man, J Auton Nerv Syst source
- Not checked yetcites [35] Pernow, 1986, Plasma neuropeptide Y-like immunoreactivity and catecholamines during various degrees of sympathetic activation in man, Clin Physiol source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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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
“The subgroups were matched according to age and sex (table 1).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > PATIENTS AND METHODS
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Some studies have indicated that patients with chronic inflammatory diseases have an increased activity of the SNS.”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > D
What the sources say
- Not checked yetcites [16] Leden, 1983, Autonomic nerve function in rheumatoid arthritis of varying severity, Scand J Rheumatol source
- Not checked yetcites [17] Kuis, 1996, The autonomic nervous system and the immune system in juvenile rheumatoid arthritis, Brain Behav Immun source
- Not checked yetcites [18] Perry, 1989, Altered autonomic function in patients with arthritis or with chronic myofascial pain, Pain source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Release of cortisol is typically coupled to release of norepinephrine, which leads to stronger signalling through the b adrenoceptor; several studies have shown cooperation of cortisol and norepinephrine at a molecular level.”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > D
What the sources say
- Not checked yetcites [22] Oikarinen, 1984, Modulation of glucocorticoid receptor activity by cyclic nucleotides and its implications on the regulation of human skin fibroblast growth and protein synthesis, Biochim Biophys Acta source
- Not checked yetcites [23] Gruol, 1986, Cyclic AMP-dependent protein kinase promotes glucocorticoid receptor function, J Biol Chem source
- Not checked yetcites [24] Nakada, 1987, Glucocorticoid regulation of beta-adrenergic receptors in 3T3-L1 preadipocytes, Mol Pharmacol
plaindirect- Asserted: passes — The authors put it forward as true.
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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
“In all subjects, blood was drawn between 08:00 and 10:00 in the morning when the patients visited the outpatient clinic.”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > Laboratory variables
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
The paper relies on this without support.
Serum levels of adrenal hormones are largely independent of sex.
“Because serum levels of adrenal hormones are largely independent of sex, male and female subjects were not further separated into subgroups.”
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
“There seems to be a dissociation between high activity of the SNS and relatively normal activity of the HPA axis in CIDs [114,115].”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [115]
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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.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > PATIENTS AND METHODS
“Patients were assigned to receive single self injections of adalimumab 40 mg subcutaneously every other week.”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > PATIENTS AND METHODS
“Anti-TNF antibodies were infused on weeks 0, 2, 4, 6, 8, 10, and 12.”
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > PATIENTS AND METHODS
“The subgroups were matched according to age and sex (table 1).”
§ Increase of sympathetic outflow measured by neuropeptide Y and decrease of the hypothalamicpituitary-adrenal axis tone in patients with systemic lupus erythematosus and rheumatoid arthritis: another example of uncoupling of response systems > DISCUSSION
“| Age (years) | 38.1 (2.1) | 37.1 (1.5) | 57.7 (1.7) | 51.5 (0.8) | | Sex, female/male (%) | 24/8 (75/25) 25/17 (60/40) 52/10 (84/16) 12/11 (52/48) | | | |”
Citations
Cites
Arnett, F. C., Edworthy, S. M., Bloch, D. A., McShane, D. J., Fries, J. F., Cooper, N. S., Healey, L. A., Kaplan, S. R., Liang, M. H., Luthra, H. S., et al. (1988) · Arthritis & Rheumatism · doi:10.1002/art.1780310302 · Cited by 19,753
The 1982 revised criteria for the classification of systemic lupus erythematosus
Tan, E. M., Cohen, A. S., Fries, J. F., Masi, A. T., Mcshane, D. J., Rothfield, N. F., Schaller, J. G., Talal, N., & Winchester, R. J. (1982) · Arthritis & Rheumatism · doi:10.1002/art.1780251101 · Cited by 14,519
Revised Criteria for the Classification of Rheumatoid Arthritis
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“This pattern has been observed in inflammatory diseases of several different types of tissues including the skin (Buske-Kirschbaum et al., 2006; Buske-Kirschbaum et al., 2002), joints (Härle et al., 2006), and gut (Straub et al., 2002).”
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Metadata
- Authors
- Härle, P., Straub, R. H., Wiest, R., Mayer, A., Schölmerich, J., Atzeni, F., Carrabba, M., Cutolo, M., & Sarzi-Puttini, P.
- Affiliations
- University Hospital Regensburg (DE)
- Luigi Sacco Hospital (IT)
- University of Genoa (IT)
- Corresponding author
- Straub, R H
- ORCID
- Cutolo, M
- Venue
- Annals of the Rheumatic Diseases
- Publisher
- Elsevier BV
- Published
- 2006-01
- Volume
- 65
- Issue
- 1
- Pages
- 51-56
- ISSN
- 0003-4967 (ISSN-L)
- PMC
- PMC1797997
- OpenAlex
- W2103734979
- Semantic Scholar
- 481ff5edd6e0c0423286f6e3f087c7d8f982432f
- Cited by
- 114
- References
- 71
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 8 · 2022: 4 · 2021: 2 · 2020: 5 · 2019: 4 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 9 · 2014: 10 · 2013: 11 · 2012: 7
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Annals of the Rheumatic Diseases (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (acceptedVersion)
- Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
- HighWire Press Open Archive (submittedVersion)
- University of Regensburg Publication Server (University of Regensburg)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- sympathetic nervous system, neuropeptide Y, hypothalamic-pituitary-adrenal axis, systemic lupus erythematosus, rheumatoid arthritis, prednisolone, ACTH, cortisol, adalimumab, anti-TNF therapy, proinflammation, autoimmunity
- MeSH terms
- Adalimumab, Adrenocorticotropic Hormone, Adult, Antibodies, Monoclonal, Arthritis, Rheumatoid, Female, Glucocorticoids, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Lupus Erythematosus, Systemic, Male, Middle Aged, Neuropeptide Y, Pituitary-Adrenal System, Prednisolone, Severity of Illness Index, Sympathetic Nervous System, Tumor Necrosis Factor-alpha, Antibodies, Monoclonal, Humanized
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.
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