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

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The Pineal Gland and Cancer

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.

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Maestroni, G.J.M. (2001). Melatonin and the Immune System Therapeutic Potential in Cancer, Viral Diseases, and Immunodeficiency States. In: Bartsch, C., Bartsch, H., Blask, D.E., Cardinali, D.P., Hrushesky, W.J.M., Mecke, D. (eds) The Pineal Gland and Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59512-7_20

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  • DOI: https://doi.org/10.1007/978-3-642-59512-7_20

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