Effects of exercise on macrophage activation for antitumor cytotoxicity

Recent evidence suggests that exercise affects macrophage functions and that amount of exercise may be important. We determined effects of moderate (MOD) and exhaustive treadmill running (EXH) on 1) ability of macrophages to become activated for antitumor cytotoxicity after injection of heat- inactivated Propionibacterium acnes in vivo, 2) macrophage responsiveness to activating agents lipopolysaccharide and interferon-γ, and 3) role of glucocorticoids and various macrophage metabolic products in modulating cytotoxicity in exercised animals. Male C3H/HeN mice were randomly assigned to MOD (18 m/min, 5% grade, 30 min/day) or EXH (18-35 m/min, 5%, 2-4 h) on a motor-driven treadmill. Control animals were kept in simulated treadmill lanes located directly over the runners. In general, both MOD and EXH increased cytotoxicity (42 and 22%, respectively, across all experiments; P < 0.05). Enhanced cytotoxicity was not due to altered macrophage adherence, tumor necrosis factor-α, interleukin-1β, or reactive oxygen species. Reactive nitrogen species were responsible for enhanced toxicity in EXH only. Macrophage cytotoxicity was further increased by lipopolysaccharide and interferon-γ to a similar maximal level that was the same in all groups. Plasma corticosterone was elevated two- and fourfold in MOD and EXH, respectively, but there was no correlation between plasma corticosterone and macrophage cytotoxicity when compared across all groups even though cells were sensitive to steroid-mediated suppression in vitro. However, consistent with a corticosterone effect, EXH reduced the number of peritoneal macrophages elicited during P. acnes inflammation and abolished the typical exercise-induced increase in cytotoxicity of activated macrophages. In summary, the effects of exercise on macrophage antitumor cytotoxicity are likely complex and dependent on exercise dosage and functional state of macrophages at the time of the exercise stimulus.