Exploring the Mechanisms Underlying Exercise-Induced Changes in Natural Killer Cell Cytotoxicity

Abstract

Natural Killer (NK) cells are cytotoxic effectors of the innate immune system that eliminate tumor cells. We have previously shown that NK cell cytotoxicity (NKCA) is enhanced by acute bouts of exercise. However, the mechanisms underlying exercise-induced changes in NKCA are not yet fully understood. Exercise-induced mobilization of highly cytotoxic NK cell subsets has been proposed as one mechanism. Alternatively, exercise increases glucocorticoid and cytokines levels, which have also been shown to alter NKCA. PURPOSE: To examine the role of shifts in proportions of NK cell subsets, cytokines, and hormones on exercise induced changes in NKCA. METHODS: Adults (n=13) cycled 30 min at 115% of their lactate threshold power. Blood was collected pre, post, and 1h post exercise. Effector cells isolated from blood were incubated with K562 or U266 tumor target cells in the presence of autologous serum. NKCA was assessed after 4h by measuring lysed target cells in a flow cytometry based assay. To investigate the effects of factors (hormones and cytokines) released during exercise, pre exercise effectors were incubated with targets in the presence of pre, post, and 1h post exercise serum. The effect of shifts in NK cell subsets was determined by incubating pre, post and 1H post exercise cells with targets in presence of pre exercise serum. We also tested the cytotoxicity of pre, post, and 1h post effectors incubated with serum from the corresponding time point. RESULTS: Autologous pre, post, and 1h post exercise serum did not cause tumor cell lysis in the absence of effectors. The cytotoxicity of pre exercise effector cells was significantly increased against U266 target cells when incubated in 1h post exercise serum (Pre vs. post vs.1H post =0.318±.039 vs. 0.334±.039 vs. 0.438±.039, p<0.05). There was no difference in cytotoxicity of pre, post, 1h post effectors incubated with pre-exercise serum (Pre vs. post vs.1H post =0.321±.046 vs. 0.282±.047 vs. 0.323±.047, p<0.05). CONCLUSION: 1h post exercise serum enhanced resting NK cell cytotoxicity, indicating that factors present in serum after acute exercise can prime effector cell function. Future work will identify levels of glucocorticoids and cytokines present in 1h post exercise serum.