ACTIVATION OF HUMAN MONOCYTES BY THE PINEAL HORMONE MELATONIN

To determine the effects of the pineal hormone melatonin on human mono cytes, human monocytes were activated by different concentrations of m elatonin. Above the activation threshold of 5 x 10(-11) M, melatonin w as able to induce the cytotoxicity of human monocytes, the secretion o f IL-1, and the production oF reactive oxygen intermediates. Melatonin and LPS seemed to have a synergistic effect on human monocyte activat ion. 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, me latonin 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 th at they were plated and then activated by melatonin (10(-12) M) 8 h la ter, no IL-1 secretion and no cytotoxicity were detected. However, whe n 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 indu ces both cell-associated IL-1 alpha and IL-1 beta activities. Below th is 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 ind uce the mRNA for both IL-1 (alpha and beta). It seems that melatonin a ctivates monocytes through protein kinase C. These data suggest that m elatonin activates monocytes and induces their cytotoxic properties, a long with the IL-1 secretion.