Short-term acetaminophen consumption enhances the exercise-induced increase in Achilles peritendinous IL-6 in humans

Through an unknown mechanism, the cyclooxygenase inhibitor and antipyretic acetaminophen (APAP) alters tendon mechanical properties in humans when consumed during exercise. Interleukin-6 (IL-6) is produced by tendon during exercise and is a potent stimulator of collagen synthesis. In nontendon tissue, IL-6 is upregulated in the presence of cyclooxygenase inhibitors and may contribute to alterations in extracellular matrix turnover, possibly due to inhibition of prostaglandin E-2 (PGE(2)). We evaluated the effects of APAP on IL-6 and PGE(2) in human Achilles peritendinous tissue after 1 h of treadmill exercise. Subjects were randomly assigned to a placebo (n = 8, 26 +/- 1 yr) or APAP (n = 8, 25 +/- 1 yr) group. Each subject completed a nonexercise and exercise experiment consisting of 6 h of microdialysis. Drug (APAP, 1,000 mg) or placebo was administered in a double-blind manner during both experiments. PGE(2) and IL-6 were determined via enzyme immunoassay and APAP via high-performance liquid chromatography. In subjects given APAP, peritendinous APAP levels increased to 4.08 +/- 0.65 mu g/ml (P < 0.05). PGE(2) did not increase with exercise in either group (P > 0.05), nor was PGE(2) significantly reduced in the APAP group. IL-6 levels increased with exercise in both groups (P < 0.05), but this increase was greater in the APAP group (P < 0.05). Our findings suggest that APAP enhances tendon IL-6 production after exercise. Peak levels of APAP obtained in the peritendinous space were twofold lower than values reported in plasma or skeletal muscle. These findings provide insight into the effects of APAP on tendon and provide novel information on the kinetics of APAP in tendon tissue after oral APAP consumption.