Georges JM Maestroni

Center for Experimental Pathology

Istituto Cantonale di patologia

6601 Locarno 1, Switzerland.

Running Head : Melatonin as immunoregulatory agent

Key Words: melatonin, melatonin receptors, T-helper, immunopharmacology, viral diseases, secondary immunodeficiency

Correspondence : Dr. Georges JM Maestroni

Center for Experimental Pathology

Istituto Cantonale di Patologia

6601 Locarno 1, Switzerland

Tel +41 91 756 26 71

Fax +41 91 756 26 90



The work performed in Locarno has been supported by Swiss Nationalfonds grants no.; 31.25350.88; 31.36128.92, 31.45532.95 and by the Helmut Horten Foundation.


The pineal neurohormone melatonin synchronizes functionally 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 g-interferon and interleukin-2, as well as of novel opioid cytokines which crossreact immunologically with both interleukin-4 and dynorphin B. Melatonin has been reported also to enhance the production of interleukin-6 from human monocytes. These mediators may counteract secondary immunodeficiences, 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, g-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.