The role of melatonin in immuno-enhancement: potential application in cancer.

Melatonin, a neurohormone produced mainly by the pineal gland, is a modulator of haemopoiesis and of immune cell production and function, both in vivo and in vitro. Physiologically, melatonin is associated with T-helper 1 (Th1) cytokines, and its administration favours Th1 priming. In both normal and leukaemic mice, melatonin administration results in quantitative and functional enhancement of natural killer (NK) cells, whose role is to mediate defenses against virus-infected and cancer cells. Melatonin appears to regulate cell dynamics, including the proliferative and maturational stages of virtually all haemopoietic and immune cells lineages involved in host defense - not only NK cells but also T and B lymphocytes, granulocytes and monocytes - in both bone marrow and tissues. In particular, melatonin is a powerful antiapoptotic signal promoting the survival of normal granulocytes and B lymphocytes. In mice bearing mid-stage leukaemia, daily administration of melatonin results in a survival index of 30-40% vs. 0% in untreated mice. Thus, melatonin seems to have a fundamental role as a system regulator in haemopoiesis and immuno-enhancement, appears to be closely involved in several fundamental aspects of host defense and has the potential to be useful as an adjuvant tumour immunotherapeutic agent.