Association of C-reactive protein and interleukin-6 with new-onset fatigue in the Whitehall II prospective cohort study

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. 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). 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 (