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Tryptophan, Serotonin, and Melatonin pp 217–226Cite as

Therapeutic Potential of Melatonin in Immunodeficiency States, Viral Diseases, and Cancer

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 467))

Abstract

Maintenance of health depends on the ability to respond appropriately to environmental Stressors via reciprocal interactions between the body and the brain. In this context, it is well recognized that the pineal hormone melatonin (MLT) plays an important role. T-helper cells bear G-protein-coupled MLT cell membrane receptors and, perhaps, MLT nuclear receptors. Activation of MLT receptors enhances the release of T-helper cell cytokines, such as γ-interferon and interleukin-2 (IL-2), as well as activation of novel opioid cytokines which crossreact immunologically with both interleukin-4 and dynorphin B. MLT has been reported also to enhance the production of interleukin-1, interleukin-6 and interleukin-12 in human monocytes. These mediators may counteract secondary immunodeficiences, protect mice against lethal viral and bacterial diseases, synergize with IL-2 against cancer and influence hematopoiesis. Hematopoiesis is influenced by MLT-induced-opioids (MIO) acting on kappa 1-opioid receptors present on bone marrow macrophages. Clinically, MLT could amplify the anti-tumoral activity of low dose IL-2, induce objective tumor regression, and prolong progression-free time and overall survival. MLT seems to be required for the effectiveness of low dose IL-2 in those neoplasias that are generally resistant to IL-2 alone. Similar findings were obtained in a study in which MLT was combined with γ-interferon in metastatic renal cell carcinoma. In addition, MLT in combination with low-dose IL-2 was able to neutralize the surgery-induced lymphocytopenia in cancer patients. IL-2 treatment in patients results in activation of the immune system and creates the most suitable biological background for MLT. The finding that MLT stimulates IL-12 production from human monocytes only if incubated in presence of IL-2 further supports this concept. On the other hand, high concentrations of MLT have been found in human breast cancer tissue. The MLT concentration, which was 3 orders of magnitude higher than that present in the plasma, correlated positively with good prognostic markers such as estrogen receptor status and nuclear grade. Whether this relates to the imunoneuroendocrine action of MLT remains to be established. Clinical studies are needed on the effect of MLT in combination with IL-2 or other cytokines in cancer patients and viral diseases including HIV-infected patients.

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Authors and Affiliations

  1. Istituto Cantonale Di Patologia, Center for Experimental Pathology, 6601, Locarno, Switzerland

    George J. M. Maestroni

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  1. George J. M. Maestroni
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Editors and Affiliations

  1. Department of Psychiatry, University of Göttingen, Göttingen, Germany

    Gerald Huether

  2. Department of Clinical Chemistry, University of Heidelberg, Heidelberg, Germany

    Walter Kochen

  3. Department of Food Chemistry, University of Hamburg, Hamburg, Germany

    Thomas J. Simat

  4. Department of Food Chemistry, University of Hamburg, Hamburg, Germany

    Hans Steinhart

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Maestroni, G.J.M. (1999). Therapeutic Potential of Melatonin in Immunodeficiency States, Viral Diseases, and Cancer. In: Huether, G., Kochen, W., Simat, T.J., Steinhart, H. (eds) Tryptophan, Serotonin, and Melatonin. Advances in Experimental Medicine and Biology, vol 467. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4709-9_28

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  • DOI: https://doi.org/10.1007/978-1-4615-4709-9_28

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7133-5

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