EFFECT OF PROLONGED CATECHOLAMINE INFUSION ON IMMUNOREGULATORY FUNCTION - IMPLICATIONS IN CONGESTIVE-HEART-FAILURE

Objectives. This study sought to characterize the effects of prolonged catecholamine infusion on immunoregulatory cell traffic and activatio n. Background. Immunoregulation has been shown to be partially control led by the sympathetic nervous system. Although shortterm. elevation o f catecholamine levels is known to alter immunoregulatory cell traffic and activation, the effects of prolonged heightened sympathetic nervo us system activity have not adequately been studied. We believe that t he alterations in immune function seen in patients with congestive hea rt failure are linked to a prolonged elevation of circulating catechol amine levels. Methods. To characterize the effects of prolonged elevat ion of catecholamine levels, rats received 4 weeks of constant infusio n of epinephrine or norepinephrine through implanted osmotic minipumps . Peripheral and splenic leukocyte subsets, T cell proliferation and i nterleukin-2 receptor expression were quanti bed. Antibody production to the novel: antigen keyhole limpet hemocyanin was assessed over the 4-week treatment period. Results. Both epinephrine and norepinephrine caused significant splenic atrophy and cardiac hypertrophy; both were blocked by propranolol. Epinephrine induced lymphocytosis; both catech olamines caused an increase in natural killer cells. In the spleen, bo th epinephrine and norepinephrine led to a dose-dependent decrease in total T cells, suppressor/cytotoxic T cells and natural killer cells a nd a significant increase in B cells. Epinephrine at the low dose enha nced mitogen-induced proliferation and interleukin-2 receptor expressi on. Norepinephrine at the low dose appeared to diminish proliferation, Epinephrine tended to inhibit IgG antibody production, whereas norepi nephrine had no effect. Conclusions. The results of our study indicate that prolonged elevation of catecholamine levels alters immune cell p roliferation and differentiation. These alterations differ greatly fro m those induced by short-term stimulation but, for the most part, para llel those found in patients with congestive heart failure. We postula te that the shifts in immunoregulatory cell type and function seen in patients with congestive heart failure are due, in part, to long-stand ing increases in circulating catecholamine levels and may play an impo rtant role in the pathogenesis and progression of disease.