The photoperiod transducer melatonin and the immune-hematopoietic system

The pineal neurohormone melatonin functionally synchronizes the organism with the photoperiod. It is now well recognized that melatonin also plays an important immunoregulatory role. T-helper cells bear G-protein coupled melatonin cell-membrane receptors and, perhaps, melatonin nuclear receptors. Activation of melatonin receptors enhances the release of T-helper cell type 1 (Th1) cytokines, such as gamma-interferon and interleukin-2, as well as of novel opioid cytokines which crossreact immunologically with both interleukin-4 and dynorphin B. Melatonin has also been reported to enhance the production of interleukin-6 from human monocytes. These mediators may counteract secondary immunodeficiencies, protect mice against lethal viral and bacterial diseases, synergize with interleukin-2 in cancer patients and influence hematopoiesis. Hematopoiesis is apparently influenced by the action of the melatonin-induced opioids on kappa-opioid receptors present on stromal bone marrow cells. Most interestingly, gamma-interferon and colony stimulating factors may modulate the production of melatonin in the pineal gland. A hypothetical pineal-immune-hematopoietic network is, therefore, taking shape. From the immunopharmacological point of view, a call is made for clinical studies on the effect of melatonin in viral disease including human immunodeficiency virus-infected patients and cancer patients. In conclusion, melatonin seems to be an important immunomodulatory hormone which deserves to be further studied to identify its relevance in immune-based diseases, its therapeutic indications, and its adverse effects.