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Indomethacin Inhibits Circulating PGE2 and Reverses Postexercise Suppression of Natural Killer Cell Activity

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OSTP Journal Article

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Defence and Civil Institute of Environmental Medicine Toronto, Ontario Canada

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Natural killer NK cells are important in combating viral infections and cancer. NK cytolytic activity NKCA is often depressed during recovery from strenuous exercise. Lymphocyte subset redistribution andor inhibition of NK cells via soluble mediators, such as prostaglandin PG E2 and cortisol, are suggested as mechanisms. Ten untrained peak O2 consumption 44.0 3.5 ml kg-1. min -1 men completed at 2-wk intervals a resting control session and three randomizeddouble-blind exercise trials after the oral administration of a placebo, the PG inhibitor indomethacin 75 mgday for 5 days, or naltrexone reported elsewhere. Circulating CD3-CD1656 NK cell counts, PGE2, cortisol, and NKCA were measured before, at 0.5-h intervals during, and at 2 and 24 h after a 2-h bout of cycle ergometer exercise 65 peak O2 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 values. With placebo treatment, total NKCA was suppressed 28 P 0.05 2 h after 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 stage CD14 monocyte numbers were elevated P 0.0001. Indomethacin treatment eliminated the postexercise increase in PGE2 concentration and completely reversed the suppression of total and per CD1656 NKCA 2 h after exercise. These data support the hypothesis that the postexercise reduction in NKCA reflects changes in circulating PGE2 rather than a differential lymphocyte redistribution.

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