Role of the pineal gland in immunity: II. Melatonin enhances the antibody response via an opiatergic mechanism.

The pineal gland constitutes a major neuroendocrine organ in the brain. It transduces exogenous signals such as circadian and seasonal variations of light and temperature into proper hormonal changes which adjust and adapt internal endocrine functions. These pineal activities seem to be exerted via circadian synthesis and release of the indoleamine melatonin, a neurohormone secreted by the pineal itself. Alteration of circadian rhythms have been associated with affective disorders, psychosomatic diseases, cancer and many other pathologies. We have reported that functional and pharmacologic inhibition of melatonin synthesis results in depressed immune functions in vivo and that exogenous, evening administration of melatonin enhances antibody formation via an antigen-activated process and also antagonizes the immunosuppressive effects of corticosterone. We communicate here findings demonstrating that (a) three different inbred strains of mice possess a clear-cut cycle of melatonin levels in serum, (b) that melatonin administered in the evening enhances primary antibody response (IgM and IgG immunoglobulins) in vivo according to a dose-response behaviour and that (c) the opioid receptors blocker naltrexone antagonizes the immunostimulatory effect of melatonin. These findings point to a fundamental immunoregulatory role of circadian melatonin and to an activity of the neurohormone via opioid peptides.