Effect of prolonged catecholamine infusion on immunoregulatory function: implications in congestive heart failure.
OBJECTIVE
This study sought to characterize the effects of prolonged catecholamine infusion on immunoregulatory cell traffic and activation.


BACKGROUND
Immunoregulation has been shown to be partially controlled by the sympathetic nervous system. Although short-term elevation of catecholamine levels is known to alter immunoregulatory cell traffic and activation, the effects of prolonged heightened sympathetic nervous system activity have not adequately been studied. We believe that the alterations in immune function seen in patients with congestive heart failure are linked to a prolonged elevation of circulating catecholamine levels.


METHODS
To characterize the effects of prolonged elevation of catecholamine levels, rats received 4 weeks of constant infusion of epinephrine or norepinephrine through implanted osmotic minipumps. Peripheral and splenic leukocyte subsets, T cell proliferation and interleukin-2 receptor expression were quantified. 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 catecholamines caused an increase in natural killer cells. In the spleen, both epinephrine and norepinephrine led to a dose-dependent decrease in total T cells, suppressor/cytotoxic T cells and natural killer cells and a significant increase in B cells. Epinephrine at the low dose enhanced mitogen-induced proliferation and interleukin-2 receptor expression. Norepinephrine at the low dose appeared to diminish proliferation. Epinephrine tended to inhibit IgG antibody production, whereas norepinephrine had no effect.


CONCLUSIONS
The results of our study indicate that prolonged elevation of catecholamine levels alters immune cell proliferation and differentiation. These alterations differ greatly from those induced by short-term stimulation but, for the most part, parallel those found in patients with congestive heart failure. We postulate that the shifts in immunoregulatory cell type and function seen in patients with congestive heart failure are due, in part, to longstanding increases in circulating catecholamine levels and may play an important role in the pathogenesis and progression of disease.
Harris
T J
TJ
Department of Medicine, Veterans Affairs Medical Center, San Diego, California 92161, USA.
Waltman
T J
TJ
Carter
S M
SM
Maisel
A S
AS
D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced; D004837:Epinephrine / Q000494:pharmacology*; D006333:Heart Failure / Q000276:immunology; D007074:Immunoglobulin G / Q000187:drug effects; D007260:Infusion Pumps; D018655:Lymphocyte Count / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D013154:Spleen / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000276:immunology*
D007074:Immunoglobulin G; D015375:Receptors, Interleukin-2; D009638:Norepinephrine; D004837:Epinephrine