Indomethacin inhibits circulating PGE(2) and reverses postexercise suppression of natural killer cell activity

Natural killer (NK) cells are important in combating viral infections and c ancer. NK cytolytic activity (NKCA) is often depressed during recovery from strenuous exercise. Lymphocyte subset redistribution and/or inhibition of NK cells via soluble mediators, such as prostaglandin (PG) E-2 and cortisol , are suggested as mechanisms. Ten untrained (peak O-2 consumption = 44.0 /- 3.5 ml.kg(-1).min(-1)) men completed at 2-wk intervals a resting control session and three randomized double-blind exercise trials after the oral a dministration of a placebo, the PG inhibitor indomethacin (75 mg/day for 5 days), or naltrexone (reported elsewhere). Circulating CD3(-)CD16(+)/56(+) NK cell counts, PGE(2), cortisol, and NKCA were measured before, at 0.5-h i ntervals during, and at 2 and 24 h after a 2-h bout of cycle ergometer exer cise (65% peak O-2 consumption). During placebo and indomethacin conditions , exercise induced significant (P < 0.0001) elevations of NKCA (>100%) and circulating NK cell counts (>350%) compared with corresponding control valu es. With placebo treatment, total NKCA was suppressed (28%; P < 0.05) 2 h a fter exercise, and a postexercise elevation (36%; P = 0.02) of circulating PGE2 was negatively correlated (r = 0.475, P = 0.03) with K-562 tumor cell lysis, NK counts were unchanged in the postexercise period, but at this sta ge CD14(+) monocyte numbers were elevated (P < 0.0001). Indomethacin treatm ent eliminated the postexercise increase in PGE(2) concentration and comple tely reversed the suppression of total and per CD16(+)56(+) NKCA 2 h after exercise. These data support the hypothesis that the post;exercise reductio n in NKCA reflects changes in circulating PGE(2) rather than a differential lymphocyte redistribution.