title: Activation of human monocytes by the pineal hormone melatonin.
abstract: To determine the effects of the pineal hormone melatonin on human monocytes, human monocytes were activated by different concentrations of melatonin. Above the activation threshold of 5 x 10(-11) M, melatonin was able to induce the cytotoxicity of human monocytes, the secretion of IL-1, and the production of reactive oxygen intermediates. Melatonin and LPS seemed to have a synergistic effect on human monocyte activation. Indeed, below their respective monocyte activation threshold (5 x 10(-11) M and 0.625 ng/ml), melatonin (10(-12) M) in association with LPS (0.2 ng/ml) was able to induce cytotoxicity, IL-1 secretion, and reactive oxygen intermediates production. Melatonin alone at 10(-12) M or LPS alone at 0.2 ng/ml did not activate monocytes. Furthermore, melatonin was able to prime the monocytes for a subsequent activation by LPS. When monocytes were activated by LPS (0.25 ng/ml) at the time that they were plated and then activated by melatonin (10(-12) M) 8 h later, no IL-1 secretion and no cytotoxicity were detected. However, when the cells were first activated by melatonin (10(-12) M), and then 8 h later by LPS (0.25 ng/ml), IL-1 secretion and monocyte cytotoxicity were observed. Above its monocyte activation threshold, melatonin induces both cell-associated IL-1 alpha and IL-1 beta activities. Below this activation threshold, i.e., at 10(-12) M, melatonin does not induce the cell-associated IL-1 alpha and IL-1 beta activities, but does induce the mRNA for both IL-1 (alpha and beta). It seems that melatonin activates monocytes through protein kinase C. These data suggest that melatonin activates monocytes and induces their cytotoxic properties, along with the IL-1 secretion.
authors.affiliation: Department of Molecular Pharmacology and Biologic Chemistry, Northwestern University Medical School, Chicago, IL 60611.
authors.forename: K M
authors.initials: KM
authors.lastname: Morrey
authors.forename: J A
authors.initials: JA
authors.lastname: McLachlan
authors.forename: C D
authors.initials: CD
authors.lastname: Serkin
authors.forename: O
authors.initials: O
authors.lastname: Bakouche
mesh_terms: D015152:Blotting, Northern; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000502:physiology*; D008550:Melatonin / Q000032:analysis / Q000502:physiology*; D009000:Monocytes / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis; D010870:Pineal Gland / Q000737:chemistry; D011493:Protein Kinase C / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D011493:Protein Kinase C; D008550:Melatonin