title: Fatigue in primary Sjögren's syndrome is associated with lower levels of proinflammatory cytokines.
abstract: OBJECTIVE
  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.
authors: Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK; Newcastle-upon-Tyne NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors: Nadia
authors: N
authors: Howard Tripp
authors: Musculoskeletal Research Group , Institute of Cellular Medicine, Newcastle University , Newcastle-upon-Tyne , UK.
authors: Jessica
authors: J
authors: Tarn
authors: Musculoskeletal Research Group , Institute of Cellular Medicine, Newcastle University , Newcastle-upon-Tyne , UK.
authors: Andini
authors: A
authors: Natasari
authors: Department of Mathematics and Statistics , Newcastle University , Newcastle-upon-Tyne , UK.
authors: Colin
authors: C
authors: Gillespie
authors: Newcastle-upon-Tyne NHS Foundation Trust , Newcastle-upon-Tyne , UK.
authors: Sheryl
authors: S
authors: Mitchell
authors: Musculoskeletal Research Group , Institute of Cellular Medicine, Newcastle University , Newcastle-upon-Tyne , UK.
authors: Katie L
authors: KL
authors: Hackett
authors: University Hospital Birmingham , Birmingham , UK.
authors: Simon J
authors: SJ
authors: Bowman
authors: Great Western Hospitals NHS Foundation Trust , Swindon , UK.
authors: Elizabeth
authors: E
authors: Price
authors: Section of Musculoskeletal Disease, NIHR Leeds Musculoskeletal Biomedical Research Unit , Leeds Institute of Molecular Medicine, University of Leeds, Leeds Teaching Hospitals Trust , Leeds , UK.
authors: Colin T
authors: CT
authors: Pease
authors: Section of Musculoskeletal Disease, NIHR Leeds Musculoskeletal Biomedical Research Unit , Leeds Institute of Molecular Medicine, University of Leeds, Leeds Teaching Hospitals Trust , Leeds , UK.
authors: Paul
authors: P
authors: Emery
authors: Nottingham University Hospitals NHS Trust , Nottingham , UK.
authors: Peter
authors: P
authors: Lanyon
authors: Gartnavel General Hospital , Glasgow , UK.
authors: John
authors: J
authors: Hunter
authors: Gartnavel General Hospital , Glasgow , UK.
authors: Monica
authors: M
authors: Gupta
authors: Barts Health NHS Trust & Barts and the London School of Medicine & Dentistry , London , UK.
authors: Michele
authors: M
authors: Bombardieri
authors: Barts Health NHS Trust & Barts and the London School of Medicine & Dentistry , London , UK.
authors: Nurhan
authors: N
authors: Sutcliffe
authors: Barts Health NHS Trust & Barts and the London School of Medicine & Dentistry , London , UK.
authors: Costantino
authors: C
authors: Pitzalis
authors: NHS Fife, Whyteman's Brae Hospital , Kirkaldy , UK.
authors: John
authors: J
authors: McLaren
authors: Royal Hampshire County Hospital , Winchester , UK.
authors: Annie
authors: A
authors: Cooper
authors: Royal Derby Hospital , Derby , UK.
authors: Marian
authors: M
authors: Regan
authors: University College London Hospitals NHS Foundation Trust , London , UK.
authors: Ian
authors: I
authors: Giles
authors: University College London Hospitals NHS Foundation Trust , London , UK.
authors: David A
authors: DA
authors: Isenberg
authors: Queen Elizabeth Hospital , Gateshead , UK.
authors: Vadivelu
authors: V
authors: Saravanan
authors: Sunderland Royal Hospital , Sunderland , UK.
authors: David
authors: D
authors: Coady
authors: Southend University Hospital , Westcliff-on-sea , UK.
authors: Bhaskar
authors: B
authors: Dasgupta
authors: Royal National Hospital for Rheumatic Diseases , Bath , UK.
authors: Neil
authors: N
authors: McHugh
authors: Portsmouth Hospitals NHS Trust , Portsmouth , UK.
authors: Steven
authors: S
authors: Young-Min
authors: Aintree University Hospitals , Liverpool , UK.
authors: Robert
authors: R
authors: Moots
authors: Basildon Hospital , Basildon , UK.
authors: Nagui
authors: N
authors: Gendi
authors: Royal Hallamshire Hospital , Sheffield , UK.
authors: Mohammed
authors: M
authors: Akil
authors: Newcastle-upon-Tyne NHS Foundation Trust , Newcastle-upon-Tyne , UK.
authors: Bridget
authors: B
authors: Griffiths
authors: Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK; Newcastle-upon-Tyne NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors: Dennis W
authors: DW
authors: Lendrem
authors: Musculoskeletal Research Group, Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK; Newcastle-upon-Tyne NHS Foundation Trust, Newcastle-upon-Tyne, UK.
authors: Wan-Fai
authors: WF
authors: Ng
keywords: Autoimmune Diseases; Cytokines; Inflammation; Sjøgren's Syndrome