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

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By By H. J. Cho et al. • • April 17, 2014

Editor's Comment: C-reactive protein is associated with inflammation, while interleukin-6 is both a pro- and anti-inflammatory cytokine. C-reactive protein is often high in ME/CFS patients, as is IL-6 (Fletcher et al, 2009, Spence et al, 2008).

By H. J. Cho et al.


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.

Source: Cho HJ, Kivimäki M, Bower JE, Irwin MR. Psychol Med. 2013 Aug;43(8):1773-83. doi: 10.1017/S0033291712002437. Epub 2012 Nov 14.

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