IMMUNE FUNCTION IN PATIENTS WITH CHRONIC STABLE CONGESTIVE-HEART-FAILURE

The objective of this study was to ascertain whether immune abnormalities were present in a group of patients with chronic stable heart failure at a time when sympathetic drive was not excessive. Elevated sympathetic tone not only plays an important role in the pathophysiologic characteristics of congestive heart failure but may also regulate certain aspects of immune function, which has been shown to be abnormal in patients with severe heart failure. Studies have indicated a high incidence of heterophil antibodies against constituents of the heart, the presence of antibody-mediated cytotoxicity against cultured heart cells, and a decrease in suppressor and natural killer-cell function in patients with idiopathic dilated cardiomyopathy. Lymphocytes were separated over a Ficoll-Hypaque gradient. Lymphocyte subtypes and well as interleukin-2 receptors were detected by means of mouse monoclonal antibodies conjugated with fluorescein or phycoerytherin, and immunofluorescence was measured with a flow cytometer. Mitogen proliferation was assessed by tritiated thymidine incorporation in the presence of either conconavalin A or tetanus toxoid. Serum was used in conjunction with iodine 125-labeled iodopindolol binding to rat cardiac membranes to attempt to detect beta-receptor antibodies. In patients with ischemic (n = 21) and idiopathic (n = 16) cardiomyopathy, the norepinephrine levels were modestly elevated (idiopathic = 482 +/- 70 pg/ml; ischemic 501 +/- 45 pg/ml) compared with control subjects without heart disease (n = 10; norepinephrine = 252 +/- 70 pg/ml). We found no differences in the number and subtypes of circulating lymphocytes in the three groups, and there was no serum inhibition of beta-binding to rat cardiac membranes. Mitogen proliferation, as well as interleukin-2 receptor expression, was unaltered when lymphocytes from all patients with congestive heart failure were exposed to the nonspecific T-cell mitogen concanavalin A. Stimulation of lymphocytes over a wide range of concentrations with the specific T-cell antigen tetanus toxoid, however, revealed decreases in H-3-thymidine incorporation both in patients with ischemic and idiopathic cardiomyopathy compared with control subjects. We conclude that early in the course of heart failure, at a time when there are no alterations in circulating lymphocytes and no evidence of antibodies against the cardiac beta-receptor, use of the specific T-cell antigen tetanus toxoid, but not the conventional mitogen concanavalin A, uncovers an abnormality in T-cell function both in patients with idiopathic and ischemic heart failure.