Background Fatigue is a common and problematic symptom in many chronic diseases including primary Sjögren's Syndrome (pSS).1,2 Although the pathophysiological basis of fatigue is not fully understood and no biomarkers have yet been identified, emerging data implicates inflammatory pathways and immune dysregulation as potential mechanistic components.3,4
Objectives The aim of this study is to investigate the relationship between cytokine levels and patient-reported levels of fatigue, using pSS as an example of a chronic immunological condition.
Methods Blood levels of 22 cytokines were measured in 161 patients with pSS from the UK Primary Sjögren's Syndrome Registry (UKPSSR) and 28 healthy non-fatigued controls.5 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 ANOVA. Logistic regression was used to determine the most important predictors of fatigue levels.
Results 13 cytokines were significantly higher in pSS patients compared to healthy controls, with a p≤0.0001 for 8 of these. Levels of four pro-inflammatory cytokines IP-10 (p=0.019), TNF-α (p=0.046), LT-α (p=0.034) and INF-γ (p=0.022) decreased with increasing fatigue in the pSS cases. Serum levels of IFN-γ and IP-10, and pain and depression scores were the best predictors of fatigue level with correct predictions of fatigue level in 67% of cases when these 4 parameters were used.
Conclusions 4 pro-inflammatory cytokines decrease as fatigue level increases in pSS patients. Research into anti-inflammatory pathways and cytokines may be insightful in understanding the pathophysiological basis of fatigue. Cytokines, pain and depression appear to be the most powerful predictors of fatigue. Further study is required to characterise the complex biochemical cascades underlying fatigue in pSS and other chronic conditions, as well as the influence of potential clinical confounding factors such as pain and depression
W. F. Ng, S. J. Bowman, Primary Sjogren's syndrome: too dry and too tired. Rheumatology 49, 844–853 (2010)
P. J. Barendregt, M. R. Visser, E. M. Smets, J. H. Tulen, A. H. van den Meiracker, F. Boomsma, H. M. Markusse, Fatigue in primary Sjogren's syndrome. Annals of the rheumatic diseases 57, 291–295 (1998)
S. Blundell, K. K. Ray, M. Buckland, P. D. White, Chronic fatigue syndrome and circulating cytokines: A systematic review. Brain, behavior, and immunity 50, 186–195 (2015)
H. I. Bax, T. M. Vriesendorp, C. G. Kallenberg, W. W. Kalk, Fatigue and immune activity in Sjogren's syndrome. Annals of the rheumatic diseases 61, 284 (2002)
W.-F. Ng, S. J. Bowman, B. Griffiths, UK Sjogren's Syndrome Group, United Kingdom Primary Sjogren's Syndrome Registry-a united effort to tackle an orphan rheumatic disease. Rheumatology 50, 32–39 (2011)
Acknowledgement We thank all of the patients and healthy volunteers who participated in this study.
Disclosure of Interest None declared