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Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines

Lookup NU author(s): Dr Jessica Tarn, Andini Natasari, Colin Gillespie, Sheryl Mitchell, Dr Katie Hackett, Dr Vadivelu Saravanan, Dr David Coady, Dr Steven Young-Min, Dr Bridget Griffiths, Dr Dennis Lendrem, Professor Fai Ng

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Objectives: This article reports relationships between serum cytokine levels and patient-reported levels of fatigue, in the chronic immunological condition primary Sjögren's syndrome (pSS). Methods: Blood levels of 24 cytokines were measured in 159 patients with pSS from the United Kingdom Primary Sjögren's Syndrome Registry and 28 healthy non-fatigued controls. Differences between cytokines in cases and controls were evaluated using Wilcoxon test. Patient-reported scores for fatigue were evaluated, classified according to severity and compared with cytokine levels using analysis of variance. Logistic regression was used to determine the most important predictors of fatigue levels. Results: 14 cytokines were significantly higher in patients with pSS (n=159) compared to non-fatigued healthy controls (n=28). While serum levels were elevated in patients with pSS compared to healthy controls, unexpectedly, the levels of 4 proinflammatory cytokines - interferon-γ-induced protein-10 (IP-10) (p=0.019), tumour necrosis factor-α ( p=0.046), lymphotoxin-α (p=0.034) and interferon-γ (IFN-γ) (p=0.022) - were inversely related to patient-reported levels of fatigue. A regression model predicting fatigue levels in pSS based on cytokine levels, disease-specific and clinical parameters, as well as anxiety, pain and depression, revealed IP-10, IFN-γ (both inversely), pain and depression (both positively) as the most important predictors of fatigue. This model correctly predicts fatigue levels with reasonable (67%) accuracy. Conclusions: Cytokines, pain and depression appear to be the most powerful predictors of fatigue in pSS. Our data challenge the notion that proinflammatory cytokines directly mediate fatigue in chronic immunological conditions. Instead, we hypothesise that mechanisms regulating inflammatory responses may be important.


Publication metadata

Author(s): Tripp NH, Tarn J, Natasari A, Gillespie C, Mitchell S, Hackett KL, Bowman SJ, Price E, Pease CT, Emery P, Lanyon P, Hunter J, Gupta M, Bombardieri M, Sutcliffe N, Pitzalis C, McLaren J, Cooper A, Regan M, Giles I, Isenberg DA, Saravanan V, Coady D, Dasgupta B, McHugh N, Young-Min S, Moots R, Gendi N, Akil M, Griffiths B, Lendrem DW, Ng W-F

Publication type: Article

Publication status: Published

Journal: RMD Open

Year: 2016

Volume: 2

Print publication date: 01/07/2016

Online publication date: 19/07/2016

Acceptance date: 24/06/2016

Date deposited: 03/05/2017

ISSN (electronic): 2056-5933

Publisher: BMJ Publishing Group

URL: https://doi.org/10.1136/rmdopen-2016-000282

DOI: 10.1136/rmdopen-2016-000282


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