The impact of performing exercise on the immune system presents contrasting effects on health when performed at different intensities. In addition, the consequences of performing chronic exercise have not been sufficiently studied in contrast to the effects of acute bouts of exercise. The porpoise of this work was to determine the effect that a popular exercise regimen (chronic/moderate/aerobic exercise) has on the proportion of different immune cell subsets, their function and if it affects the cannabinoid system with potentially functional implications on the immune system. A marked increase in several immune cell subsets and their expression of cannabinoid receptors was expected, as well as an enhanced proliferative and cytotoxic activity by total splenocytes in exercised animals. For this study male Wistar rats performed treadmill running 5 times a week for a period of 10 weeks, at moderate intensity. Our results showed a significant decrease in lymphocyte subpopulations (CD4+, Tγδ, and CD45 RA+ cells) and an increase in the cannabinoid receptors expression in those same cell. Although functional assays did not reveal any variation in total immunoglobulin production or NK cells cytotoxic activity, proliferative capability of total splenocytes increased in trained rats. Our results further support the notion that exercise affects the immunological system and extends the description of underlying mechanisms mediating such effects. Altogether, our results contribute to the understanding of the benefits of exercise on the practitioner´s general health.

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22The impact of performing exercise on the immune system presents contrasting effects on health when 23 performed at different intensities. In addition, the consequences of performing chronic exercise have 24 not been sufficiently studied in contrast to the effects of acute bouts of exercise. Our findings shed 25 light on the effects that chronic exercise elicits on several immune cell subpopulations, from the 26 innate to the adaptive immunity. For this study male Wistar rats performed treadmill running 5 times 27 a week for a period of 10 weeks, speed and duration in each exercise bout was gradually increased 28 until reaching 40 minutes at 15 m/min. Our results showed a significant decrease in lymphocyte 29 subpopulations (CD4+, Tγδ, and CD45 RA+ cells) and also indicate an alteration in the cannabinoid 30 receptors expression in some of these cells subsets. Although functional assays did not reveal any 31 variation in total immunoglobulin production or NK cells cytotoxic activity, proliferative capability 32 of total splenocytes increased in trained rats. Our results further support the notion that exercise 33 affects the immunological system and extends the description of underlying mechanisms mediating 34 such effects. Altogether, our results contribute to the understanding of the benefits of exercise on the 35 practitioner´s general health. 37 Introduction38 The beneficial impact of exercise on the practitioner's general health is a well-known fact [1][2][3].39 Studies suggesting a connection between physical activity and the improvement of health have 40 generated information that ranges from describing adipose tissue loss to changes in genetic 41 expression [4,5]. It is well known that the immune system (IS) is critical to maintain health, and 42 whether it is enhanced or hindered when performing exercise is still controversial. Its proper 3 43 composition and its correct function will allow it to actively overcome challenges that otherwise 44 would compromise the organism's health such as infections, autoimmune diseases, cancer, etc. 45 46 Data regarding the changes induced by exercise in cell subpopulations of the IS and their function 47 seems to be controversial [6][7][8]. This may be partly explained by the use of different exercise 48 paradigms. Along with this idea, many studies document the immediate changes on the IS induced by 49 a single bout of exercise, as opposed to the effects of its chronic performance, which suggest 50 different outcomes and in some cases opposite effects over the IS [8][9][10]. Less attention has been 51 paid to such studies and to the long-term alterations that it may produce on the IS. For instance, 52 macrophages extracted from mice trained for 12 weeks exhibited increased phagocytic activity, 53 superoxide anion production and glucose consumption when compared to macrophages obtained 54 from sedentary mice [8]. Consistently other studies have shown that chronic exercise alters the 55 function of T cells, affecting their production of pro-and anti-inflammatory cytoki...