Melatonin: modes of action within the immune system

The aim of the present project was to elucidate mechanisms underlying the strong immunoprotective effect of melatonin against alpha-adrenergic stress, as was shown in one of our previous FWF projects (P9925-Med). In view of recent results from other groups, we focussed our efforts within the present project at two possible mechanisms, i.e. an inhibitory interaction of melatonin with calmodulin, and the reported antioxidative properties of this hormone. Our results showed that melatonin did not influence the effects of calmodulin in lymphocytes, which contradicts the notion put forward by others that melatonin is a general calmodulin antagonist. Furthermore, we could show in isolated human peripheral blood lymphocytes that melatonin exhibits a slight antioxidant effect, which, however, was much weaker than the ones obtained with vitamin E (Trolox) or N-acetylserotonin (NAS), i.e. the immediate precursor of melatonin. In Jurkat cells, a human leukemic T-cell line, melatonin even exhibited a strong prooxidant activity. These partly provocative results were recently published and met considerable international interest, but they could not explain the above mentioned immunoprotective effects of melatonin in vivo. A further project is in preparation to investigate the possible role of melatonin receptors of lymphocytes. Finally, we also investigated lymphoid organs of the rat for their potential to synthesise melatonin. Using the RT- PCR method, only gut, testis, spinal cord, raphe nuclei, stomach fundus and striatum were found to yield reliable signals for both key enzymes (NAT and HIOMT) of melatonin synthesis. Very low levels of the HIOMT messages in lymphoid organs, however, indicated a limited significance of melatonin synthesis within the immune system.