Exercise can be pyrogenic in humans.

Exercise increases mean body temperature (T(body)) and cytokine concentrations in plasma. Cytokines facilitate PG production via cyclooxygenase (COX) enzymes, and PGE(2) can mediate fever. Therefore, we used a COX-2 inhibitor to test the hypothesis that PG-mediated pyrogenicity may contribute to the raised T(body) in exercising humans. In a double-blind, cross-over design, 10 males [age: 23 yr (SD 5), Vo(2 max): 53 ml x kg(-1) x min(-1) (SD 5)] consumed rofecoxib (50 mg/day; NSAID) or placebo (PLAC) for 6 days, 2 wk apart. Exercising thermoregulation was measured on day 6 during 45-min running ( approximately 75% Vo(2 max)) followed by 45-min cycling and 60-min seated recovery (28 degrees C, 50% relative humidity). Plasma cytokine (TNF-alpha, IL-10) concentrations were measured at rest and 30-min recovery. T(body) was similar at rest in PLAC (35.59 degrees C) and NSAID (35.53 degrees C) and increased similarly during running, but became 0.33 degrees C (SD 0.26) lower in NSAID during cycling (37.39 degrees C vs. 37.07 degrees C; P = 0.03), and remained lower throughout recovery. Sweating was initiated at T(body) of approximately 35.6 degrees C in both conditions but ceased at higher T(body) in PLAC than NSAID during recovery [36.66 degrees C (SD 0.36) vs. 36.39 degrees C (SD 0.27); P = 0.03]. Cardiac frequency averaged 6 x min(-1) higher in PLAC (P < 0.01), whereas exercising metabolic rate was similar (505 vs. 507 W x m(-2); P = 0.56). A modest increase in both cytokines across exercise was similar between conditions. COX-2 specific NSAID lowered exercising heat and cardiovascular strain and the sweating (offset) threshold, independently of heat production, indicating that PGE-mediated inflammatory processes may contribute to exercising heat strain during endurance exercise in humans.