Activation of human monocytes by the pineal hormone melatonin

• Published in: The Journal of immunology (1950) Vol. 153; no. 6; pp. 2671 - 2680
• Main Authors: Morrey, KM, McLachlan, JA, Serkin, CD, Bakouche, O
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.09.1994
• Subjects: Blotting, Northern; Cells, Cultured; Cytotoxicity Tests, Immunologic; Humans; Interleukin-1 - biosynthesis; Lipopolysaccharides - pharmacology; Macrophage Activation - physiology; Melatonin - analysis; Melatonin - physiology; Monocytes - physiology; Nitric Oxide - biosynthesis; Pineal Gland - chemistry; Protein Kinase C - metabolism; Reactive Oxygen Species - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.153.6.2671

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.