Prolonged Isoproterenol Treatment Alters Immunoregulatory Cell Traffic and Function in the Rat

Abstract

The mechanisms by which the sympathetic nervous system modulates functional parameters of the immune system have not been fully defined. In vivo, acute and chronic β2-adrenergic stimulation have been shown to have dramatic but opposing effects on circulating lymphocyte number and subset distribution in humans. In vitro studies have suggested impairment of numerous lymphocyte effector functions in the presence of catecholamines. To better define the effects of short and long term β-adrenergic stimulation on lymphocyte migration patterns between circulating and splenic pools, as well as function, we infused rats with either low or high doses of isoproterenol over various time intervals. Specifically, we determined the number and subset composition of peripheral blood and splenic lymphocytes in addition to assessing responsivity to the T cell mitogen concanavalin A and antibody production. As a measure of in vivo lymphocyte proliferation. we also monitored the effect of these infusions on the number of peripheral blood lymphocytes and splenocytes and the splenic weight. Isoproterenol led to dose-dependent, short-lived decrements in mitogen-induced lymphocyte proliferation with concomitant decreases in circulating and splenic lymphocyte number in a subset-specific manner. Analysis of the distribution of circulating and splenic subtypes with isoproterenol treatment suggests definite but limited influences on β-adrenergic stimulation on immunoregulatory cell traffic. We conclude that β-adrenergic stimulation in the rat model leads to a dose-dependent, transient effect on lymphocyte proliferation and migration patterns. The relative lack of functional β-receptors on rat lymphocytes and the propensity for early sustained receptor densensitization on exposure to agonist may account for qualitative differences seen between rats and humans.