Impaired β-adrenergic control of immune function in patients with chronic heart failure:: reversal by β1-blocker treatment

Background In patients with chronic heart failure (CHF) and heightened sympathetic activity alterations in immune function have been described. Objectives To find out whether, in CHF patients, P-blocker treatment might beneficially affect immune function. Methods We studied activation of circulating lymphocytes (assessed as concanavalin A (CON A)-induced inositol phosphate (IP) formation and proliferation ([H-3]-thymidine incorporation) from 8 CHF patients on standard medication (Group A, mean age 54 +/- 6 yrs, NYHA class II - IV, mean 3.1 +/- 0.3) and in 9 CHF patients on standard medication and additional treatment with the beta (1)-blocker metoprolol (Group B, mean age: 56 +/- 3 yrs, NYHA class II - IV, mean 2.9 +/- 0.2); 8 age-matched healthy volunteers (mean age 49 +/- 3 yrs) served as controls. Results Compared to controls, in group A isoprenaline-induced lymphocyte cyclic AMP-increase was reduced, CON A-evoked IP formation significantly enhanced and isoprenaline-induced inhibition of CON A-evoked IP forma tion and proliferation almost abolished. In group B, however, all these parameters were not significantly different from controls. Conclusion In CHF patients lymphocyte cyclic AMP response to beta -adrenoceptor stimulation is blunted and the inhibitory effect of cyclic AMP on lymphocyte activation is almost abolished; this could result in a non-regulated increased production and release of proinflammatory cytokines that might contribute to the progression of the disease. Chronic treatment of CHF patients with the beta (1)-blocker metoprolol (at least partly) restores lymphocyte cyclic AMP responses to beta -adrenoceptor stimulation and the inhibitory effects of cyclic AMP on lymphocyte activation; the resulting normalization of the immune function might contribute to the beneficial effects of beta (1)-blockers in treatment of CHF.