Melatonin-Induced Hematopoietic-Neuroendocrine Cytokines

  • Georges J. M. Maestroni

Abstract

We have reported that melatonin may rescue bone marrow cells from apoptosis induced either in vivo or in vitro by cancer chemotherapy compounds. The number of granulocyte-macrophage colony-forming units cultured with suboptimal concentrations of colony stimulating factor was higher in presence of melatonin both at physiological and pharmacological concentration. CD4+,Thy-1.2+cells depletion or addition of anti mouse interleukin-4 (IL-4) monoclonal antibodies prevented both effects of melatonin. We proposed that melatonin represents a neuroendocrine regulator of IL-4 production in bone marrow T-helper cells and that IL-4 stimulates adherent stromal cells to produce granulocyte/macrophage colony-stimulating factor. However, in further investigations we did not find any direct evidence of the ability of melatonin to stimulate IL4. We found that beside anti-IL4 antibodies also the specific opioid antagonist naltrexone neutralized the colony stimulating activity of melatonin. SDS-PAGE and blotting analysis of gel filtration fractions of supernatants from bone marrow cells cultures revealed that upon melatonin stimulation, T-helper cells release a 15 and 67 kDa opioid peptides which are recognized both by anti-common opioid sequence and anti-IL4 monoclonal antibodies. The term “neuroendocrine cytokines” seems thus to fit the properties of these IL4-like and opioid-like melatonin-induced peptides which might represent a new family of immunological and hematopoietic regulators.

Keywords

Toxicity Filtration Electrophoresis Polyacrylamide Melatonin 

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Copyright information

© Plenum Press, New York 1996

Authors and Affiliations

  • Georges J. M. Maestroni
    • 1
  1. 1.Center for Experimental PathologyIstituto Cantonale di PatologiaLocarnoSwitzerland

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