Impaired beta-adrenergic control of immune function in patients with chronic heart failure: reversal by beta(1)-blocker treatment

Background In patients with chronic heart failure (CHF) and heightened symp athetic activity alterations in immune function have been described. Object ives To find out whether, in CHF patients, P-blocker treatment might benefi cially 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 CH F patients on standard medication (Group A, mean age 54 +/- 6 yrs, NYHA cla ss 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, mea n age: 56 +/- 3 yrs, NYHA class II - IV, mean 2.9 +/- 0.2); 8 age-matched h ealthy volunteers (mean age 49 +/- 3 yrs) served as controls. Results Compa red to controls, in group A isoprenaline-induced lymphocyte cyclic AMP-incr ease was reduced, CON A-evoked IP formation significantly enhanced and isop renaline-induced inhibition of CON A-evoked IP forma tion and proliferation almost abolished. In group B, however, all these parameters were not signi ficantly different from controls. Conclusion In CHF patients lymphocyte cyc lic AMP response to beta -adrenoceptor stimulation is blunted and the inhib itory effect of cyclic AMP on lymphocyte activation is almost abolished; th is could result in a non-regulated increased production and release of proi nflammatory cytokines that might contribute to the progression of the disea se. Chronic treatment of CHF patients with the beta (1)-blocker metoprolol (at least partly) restores lymphocyte cyclic AMP responses to beta -adrenoc eptor stimulation and the inhibitory effects of cyclic AMP on lymphocyte ac tivation; the resulting "normalization" of the immune function might contri bute to the beneficial effects of beta (1)-blockers in treatment of CHF.