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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., Method: 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.

Objective: Causal attribution influences symptom experience, help-seeking behaviour and prognosis in chronic fatigue syndrome. We compared causal attribution of patients with unexplained chronic fatigue (UCF) in Brazil and Britain., Method: Primary care attenders in São Paulo (n = 3914) and London (n = 2459) were screened for the presence of UCF. Those with UCF (São Paulo n = 452; London n = 178) were assessed for causal attribution (physical vs. psychosocial), perceived chronicity (i.e. reported duration of fatigue) and disability., Results: British UCF patients were more likely to attribute their fatigue to physical causes (adjusted odds ratio 1.70, P = 0.037) and perceived their fatigue to be more chronic (adjusted beta 0.15, P = 0.002). There was no significant difference in current disability (adjusted beta -0.01, P = 0.81)., Conclusion: Despite similar disability levels, UCF patients in different cultural settings presented different attributions and perceptions about their illness. Sociocultural factors may have an important role in shaping illness attribution and perception around chronic fatigue.