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

Summary

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, β-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 ([³H]-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 β₁-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 formation 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 β-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 β₁-blocker metoprolol (at least partly) restores lymphocyte cyclic AMP responses to β-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 β₁-blockers in treatment of CHF.