Indomethacin modulates circulating cytokine responses to strenuous exercise in humans

Physical stress is associated with circulating cytokinemia. However the mechanisms of cytokine regulation during such stress are not clearly defined. Non-steroidal anti-inflammatory drugs (NSAIDs), including indomethacin, are widely used in countering the effects of excessive exercise, but their impact on circulating pro- and anti-inflammatory cytokine production in healthy humans also remains unclear. This study investigated the effect of five days of oral indomethacin treatment (75 mg per day) on the serum concentrations of IL-6, IL-10, IL-12, and TNF-alpha induced by exercising healthy volunteers. The results demonstrate that indomethacin does not alter resting serum cytokine concentrations. Increased circulating levels were noted, however, for all four cytokines with exercise, but with a different time-course. During and after strenuous physical exercise, indomethacin treatment blunted serum IL-6, and augmented TNF-alpha and IL-10. These findings may have important implications for both host defense and the injuries associated with excessively vigorous exercise.