Dynamic exercise increases the number of j-adrenergic receptors in mixed lymphocytes by a mechanism that is incompletely understood. In a set of in vivo studies, we have investigated the effects of dynamic exercise on the subset distribution of circulating lymphocytes and on the number of fJ-adrenergic receptors in each of these subsets in two groups of patients. In healthy subjects, exercise increased plasma norepinephrine and epinephrine and caused lymphocytosis. Whereas the number of The,lper cells increased only modestly, the number of Tsuppressoricytotoxic and natural killer cells more than tripled. The number of f-adrenergic receptors varied among subsets but was not significantly altered by dynamic exercise in any subset except natural killer cells (35% increase, p=0.0302). In a group of patients with congestive heart failure, dynamic exercise increased plasma norepinephrine but did not alter plasma epinephrine and did not cause significant lymphocytosis. We did not detect any significant alterations of circulating leukocyte subsets or /3-adrenergic receptors in any of these subsets after exercise. A combined analysis of healthy patients and heart failure patients revealed a significant correlation between increases in plasma epinephrine and increases in circulating lymphocytes. We conclude that the exercise-induced increase in /8-adrenergic receptors of mixed lymphocytes is predominantly caused by a redistribution of circulating cell subsets that differ in their 3-adrenergic receptor number. This appears to be mediated by epinephrine rather than norepinephrine. (Circulation 1990;82:2003-2010 It is well documented that prolonged exposure to agonists decreases the number of /3-adrenergic receptors in cultured cells and solid tissues of animals and humans in vitro and in ViVO.1-3 Such downregulation also occurs in human lymphocytes after prolonged treatment with 13-adrenergic agonists.

BACKGROUND The relation between the sympathetic nervous system and the immune system has not been fully defined. Recent investigations have suggested an adrenergically driven efflux of specific beta 2-receptor-rich lymphocyte subsets into the circulation with either exercise or infusion of exogenous catecholamines. METHODS AND RESULTS To determine whether acute sympathetic stimulation mediates immunoregulatory cell traffic and function via a beta 2-receptor mechanism, we exercised 20 healthy volunteers before and after 1 week of treatment with either the nonselective beta-antagonist propranolol or the beta 1-selective antagonist metoprolol. Before treatment, exhaustive exercise according to the Bruce protocol led to a marked lymphocytosis. Tsuppressor/cytotoxic (Ts/c) and natural killer cells, subtypes with the largest density of beta-receptors, showed the most pronounced increases after exercise, with less impressive elevations in T(helper) and B cells. With respect to function, exhaustive exercise led to a decrease in concanavalin A-stimulated IL-2 receptor expression and [3H]thymidine incorporation while enhancing natural killer cell activity. One week of propranolol therapy blunted the exercise-induced increases in circulating Ts/c and natural killer subpopulations as well as the previously observed alterations in cellular immune function. Treatment with the beta 1-selective antagonist metoprolol, however, did not impair the influence of exercise on any of the above parameters. CONCLUSIONS Acute sympathetic stimulation by exhaustive exercise leads to selective release of immunoregulatory cells into the circulation with subsequent alterations in cellular immune function, either secondary to subset changes or as a result of direct catecholamine effects on function. These changes are attenuated by propranolol but not metoprolol, suggesting a beta 2-mediated mechanism.