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Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines
  1. Nadia Howard Tripp1,2,
  2. Jessica Tarn1,
  3. Andini Natasari1,
  4. Colin Gillespie3,
  5. Sheryl Mitchell2,
  6. Katie L Hackett1,
  7. Simon J Bowman4,
  8. Elizabeth Price5,
  9. Colin T Pease6,
  10. Paul Emery6,
  11. Peter Lanyon7,
  12. John Hunter8,
  13. Monica Gupta8,
  14. Michele Bombardieri9,
  15. Nurhan Sutcliffe9,
  16. Costantino Pitzalis9,
  17. John McLaren10,
  18. Annie Cooper11,
  19. Marian Regan12,
  20. Ian Giles13,
  21. David A Isenberg13,
  22. Vadivelu Saravanan14,
  23. David Coady15,
  24. Bhaskar Dasgupta16,
  25. Neil McHugh17,
  26. Steven Young-Min18,
  27. Robert Moots19,
  28. Nagui Gendi20,
  29. Mohammed Akil21,
  30. Bridget Griffiths2,
  31. Dennis W Lendrem1,2 and
  32. Wan-Fai Ng1,2
  33. on behalf of the United Kingdom Primary Sjögren's Syndrome Registry
  1. 1Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK
  2. 2Newcastle-upon-Tyne NHS Foundation Trust, Newcastle-upon-Tyne, UK
  3. 3Department of Mathematics and Statistics, Newcastle University, Newcastle-upon-Tyne, UK
  4. 4University Hospital Birmingham, Birmingham, UK
  5. 5Great Western Hospitals NHS Foundation Trust, Swindon, UK
  6. 6Section of Musculoskeletal Disease, NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Institute of Molecular Medicine, University of Leeds, Leeds Teaching Hospitals Trust, Leeds, UK
  7. 7Nottingham University Hospitals NHS Trust, Nottingham, UK
  8. 8Gartnavel General Hospital, Glasgow, UK
  9. 9Barts Health NHS Trust & Barts and the London School of Medicine & Dentistry, London, UK
  10. 10NHS Fife, Whyteman's Brae Hospital, Kirkaldy, UK
  11. 11Royal Hampshire County Hospital, Winchester, UK
  12. 12Royal Derby Hospital, Derby, UK
  13. 13University College London Hospitals NHS Foundation Trust, London, UK
  14. 14Queen Elizabeth Hospital, Gateshead, UK
  15. 15Sunderland Royal Hospital, Sunderland, UK
  16. 16Southend University Hospital, Westcliff-on-sea, UK
  17. 17Royal National Hospital for Rheumatic Diseases, Bath, UK
  18. 18Portsmouth Hospitals NHS Trust, Portsmouth, UK
  19. 19Aintree University Hospitals, Liverpool, UK
  20. 20Basildon Hospital, Basildon, UK
  21. 21Royal Hallamshire Hospital, Sheffield, UK
  1. Correspondence to Dr Wan-Fai Ng; Wan-Fai.Ng{at}


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.

  • Sjøgren's Syndrome
  • Inflammation
  • Cytokines
  • Autoimmune Diseases

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See:

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