Impaired beta-adrenergic control of immune function in patients with chronic heart failure: reversal by beta1-blocker treatment.
BACKGROUND
In patients with chronic heart failure (CHF) and heightened sympathetic activity alterations in immune function have been described.


OBJECTIVE
To find out whether, in CHF patients, beta-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 beta1-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.


CONCLUSIONS
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 beta1-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 beta1-blockers in treatment of CHF.
Werner
C
C
Institute of Pharmacology and Toxicology, Martin-Lurther-University of Halle-Wittenberg, Saale, Germany.
Werdan
K
K
Pönicke
K
K
Brodde
O E
OE
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D003208:Concanavalin A / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007295:Inositol Phosphates / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D018342:Receptors, Adrenergic, beta-1 / Q000627:therapeutic use*
D000319:Adrenergic beta-Antagonists; D007295:Inositol Phosphates; D018342:Receptors, Adrenergic, beta-1; D003208:Concanavalin A; D000242:Cyclic AMP; D009638:Norepinephrine; D004837:Epinephrine