Human immune reactivity to acute and chronic exercise, regulation of natural killer cell activity by cytokines and prostaglandins

grantor: University of TorontoThe objective of this thesis was to investigate the relationships between acute physical activity, physical fitness, and immune function. To that end, three studies were undertaken: study I was to ascertain whether aerobic fitness was related to phenotypic and functional markers of immunity, as measured in a cross-section of trained ('n' = 7) ' vs'. untrained ('n' = 6) male volunteers (mean ± SD; V&d2;O2peak : 57.0 ± 6.1 'vs'. 39.0 ± 4.5 mL . kg-1 . min-1, respectively); study II was designed to compare baseline and exercise-induced (1 h @ 60% V&d2;O2peak ) changes in mitogen-stimulated lymphocyte proliferation, receptor expression and 'in vitro' elicited cytokine production in previously sedentary males ('n' = 9) before and after a 12-wk aerobic exercise training program ( V&d2;O2peak : 40.6 ± 2.8 'vs'. 49.2 ± 1.3 mL . kg-1 . min-1, respectively) 'vs'. matched controls ('n' = 6); and study III was a double-blind, placebo-controlled cross-over experiment, undertaken to examine the mechanistic roles of cytokines and prostaglandins (PGs), in the regulation of lymphocyte re-distribution and natural killer (NK) cell activity, in moderately active ( V&d2;O2peak : 44.0 ± 3.5 mL . kg-1 . min-1) males ('n' = 10) who acted as their own controls, in response to 2 h of cycle-ergometer exercise (65% V&d2;O2peak ), with and without indomethacin treatment. Data from the cross-sectional and longitudinal studies indicate a strong relationship between measures of aerobic fitness and several immune parameters. Comparisons before and after training show that 16+/56+ NK cell numbers are elevated in trained individuals, and that acute fluctuations in lymphocyte subsets (CD3+4+, CD3+8 +, CD19+), activation markers (CD25+, CD122+), lymphocyte proliferation, and IL-2 release, are blunted after training. These changes indicate that moderate endurance training may influence host defence. A modest plasma cytokinemia (IL-6, TNF-Ã, IL-10, IL-12) was detected during 2 h of cycling, but significant increases in PGE 2 did not occur until recovery. Elevations of PGE2 were blocked by 'in vivo' treatment with indomethacin. It is concluded, that changes in circulating cytokines and PGE2 during prolonged concentric exercise are consistent with the hypothesis that these soluble mediators contribute to both exercise-induced increases and post-exercise suppression of NK activity. Future studies analyzing cytolytic activity of purified populations of NK cells are necessary to resolve outstanding controversy concerning this mechanistic issue.Ph.D