Beta-blockade enhances adrenergic immunosuppression in rats via inhibition of melatonin release.

We have recently shown in rats that an in vivo treatment with catecholamines via alpha 2-receptors leads to a pronounced suppression of T- and B-cell mitogen responses of peripheral blood lymphocytes (PBL), provided that a beta-blocker is administered concomitantly. Since melatonin (MEL) reportedly has stress-protective effects on several immune functions, and since the release of MEL from the pineal gland is inhibited by beta-blockade, we tested the effect of MEL substitution on T- and B-cell mitogen responses of PBL in rats treated with two s.c. implanted retard tablets containing noradrenaline (NA) and propranolol. It was found that an oral treatment with MEL (about 40 micrograms/animal) abolished the adrenergic immunosuppression. Furthermore, functional pinealectomy induced by constant light had a similar enhancing effect on the alpha 2-adrenergic immunosuppression as observed with beta-blockers, whereas PBL from animals kept at the regular light/dark interval were resistant to the treatment with the selective alpha 2-agonist clonidine. It is concluded that endogenous MEL effectively protects rat PBL from adrenergic immunosuppression, and that beta-blockers enhance the immunosuppressive property of alpha 2-adrenergic agents via blocking the night-time release of MEL.