title: Association of C-reactive protein and interleukin-6 with new-onset fatigue in the Whitehall II prospective cohort study.
abstract: BACKGROUND
  Although basic research on neuroimmune interactions suggests that inflammatory processes may play a role in the development of fatigue, population-based evidence on this association is limited. This study examined whether plasma C-reactive protein (CRP) and interleukin-6 (IL-6), biomarkers of systemic inflammation, predict fatigue onset.
  
  
  METHODS
  The Whitehall II study is a large-scale cohort study conducted in 20 civil service departments in London. Plasma CRP and IL-6 were measured in 4847 non-fatigued participants at phase 3 (1991-1993, aged 39-63 years). Fatigue was assessed using the Vitality subscale of the 36-item Short Form Health Survey (SF-36) at phase 3 and phase 4 (1995-1996).
  
  
  RESULTS
  During a mean follow-up of 3.1 years, 957 new fatigue cases (19.7%) were identified using the pre-established cut-off score of ≤ 50 on the Vitality subscale. CRP values were dichotomized as low (<1.0 mg/l ) or high (≥ 1.0 mg/l) using the Centers for Disease Control/American Heart Association recommendations. Similarly, IL-6 values were also dichotomized as low (<1.5 pg/ml) or high (≥ 1.5 pg/ml). After full adjustment for sociodemographic and biobehavioral covariates, the odds ratios for new-onset fatigue were 1.28 [95% confidence interval (CI) 1.09-1.49, p = 0.003] for high CRP and 1.24 (95% CI 1.06-1.45, p = 0.008) for high IL-6. Similar results were found when CRP and IL-6 were treated as continuous variables.
  
  
  CONCLUSIONS
  Plasma CRP and IL-6 were prospectively associated with new-onset fatigue, supporting the hypothesis that low-grade inflammation has a role in the development of fatigue.
authors.affiliation: Cousins Center for Psychoneuroimmmunology, UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA. hjcho@mednet.ucla.edu
authors.forename: H J
authors.initials: HJ
authors.lastname: Cho
authors.forename: M
authors.initials: M
authors.lastname: Kivimäki
authors.forename: J E
authors.initials: JE
authors.lastname: Bower
authors.forename: M R
authors.initials: MR
authors.lastname: Irwin
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000096:biosynthesis*; D003430:Cross-Sectional Studies; D005221:Fatigue / Q000097:blood* / Q000209:etiology* / Q000473:pathology; D015673:Fatigue Syndrome, Chronic / Q000097:blood / Q000209:etiology / Q000473:pathology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008131:London; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D015850:Interleukin-6; D002097:C-Reactive Protein