Reduced levels of antiinflammatory cytokines in patients with chronic widespread pain

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Abstract
The term chronic widespread pain refers to a group of painful diseases of poorly understood pathophysiology. One major subgroup is fibromyalgia (FM), as defined by the criteria of the American College of Rheumatology. Among other hypotheses, a potential pathophysiologic role of cytokines in chronic widespread pain has been proposed. We undertook this study to investigate whether cytokine profiles differ in patients with chronic widespread pain and controls. We analyzed cytokine expression patterns in 40 patients with chronic widespread pain (26 of whom had FM), 40 age- and sex-matched healthy controls, and an additional 15 patients with chronic widespread pain who were recruited from a different center. Expression of messenger RNA (mRNA) for interleukin-2 (IL-2), IL-4, IL-8, IL-10, tumor necrosis factor α (TNFα), and transforming growth factor β1 (TGFβ1) in peripheral blood was analyzed using quantitative real-time polymerase chain reaction (PCR). Serum protein levels were measured by enzyme-linked immunosorbent assay. We found significantly lower relative gene expression (P < 0.0001 for IL-4; P = 0.03 for IL-10) and lower levels of serum protein concentrations (P < 0.0001 for IL-4; P = 0.04 for IL-10) of the Th2 cytokines IL-4 and IL-10 in patients with chronic widespread pain than in the control group. This finding was corroborated in an additional group of 15 patients with chronic widespread pain. There were no significant differences between the groups in levels of mRNA for IL-2, IL-8, TNFα, or TGFβ1. Protein data paralleled the real-time PCR results. Chronic widespread pain is associated with a lack of antiinflammatory and analgesic Th2 cytokine activity, which may contribute to its pathogenesis.