Lack of calmodulin antagonism of melatonin in T-lymphocyte activation

Despite various reported effects of the pineal hormone melatonin on the immune system, its mechanism of action on immune cells is still unknown. Since melatonin has been suggested as a physiological antagonist to calmodulin in certain cell types, we investigated effects of melatonin on calmodulin-dependent IL-2 production and proliferation of activated T-lymphocytes. It was found, however, that, in contrast to the calmodulin antagonists trifluoperazine and W7, melatonin neither inhibited the IL-2 production of activated lymphoblastoid Jurkat T-cells nor decreased the mitogen response of peripheral blood mononuclear leukocytes. Preincubation of Jurkat cells with melatonin did not influence trifluoperazine effects on IL-2 production indicating that melatonin does not bind to the same sites of calmodulin as trifluoperazine, as has been postulated. In conclusion, these results did not give any evidence for a calmodulin antagonism of melatonin in T-lymphocyte activation. Thus, melatonin as a calmodulin antagonist appears not to be a universal phenomenon.