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Melatonin and the Immune System Therapeutic Potential in Cancer, Viral Diseases, and Immunodeficiency States

  • Georges J. M. Maestroni
Chapter

Abstract

Neuroimmunomodulation refers to the continuous interaction between the nervous and immune systems. It is now well recognized that a main actor of this connection is the pineal hormone melatonin. T helper (Th) 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 interferon-γ(IFN-γ) and interleukin-2 (IL-2), as well as of novel opioid cytokines which crossreact immunologically with both interleukin-4 (IL-4) and dynorphin. Melatonin has been reported to also enhance the production of interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-12 (IL-12) in human monocytes. These mediators may counteract stress-induced immunodepression and other secondary immunodeficiencies, protect mice against lethal viral and bacterial diseases, synergize with interleukin-2 (IL-2) in cancer patients, and influence hematopoiesis. In cancer patients, melatonin seems to be required for the effectiveness of low-dose IL-2 in neoplasias that are generally resistant to IL-2 alone. Hematopoiesis is apparently influenced by the action of the melatonin-induced-opioids (MIO) on κ-opioid receptors present on stromal bone marrow macrophages. Most interestingly, IFN-γ and colony-stimulating factors (CSFs) may modulate the production of melatonin in the pineal gland. A hypothetical pineal-immune-hematopoietic network is therefore taking shape. From the immunopharmacological and ethical point of view, clinical studies on the effect of melatonin in combination with IL-2 or other cytokines in viral disease including human immunodeficiency virus-infected patients and cancer patients are needed. In conclusion, melatonin seems to play a crucial role in the homeostatic interactions between the brain and the immune-hematopoietic system and deserves to be further studied to identify its therapeutic indications and its adverse effects.

Keywords

Pineal Gland Melatonin Receptor Melatonin Administration Exogenous Melatonin Endogenous Melatonin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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  • Georges J. M. Maestroni

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