Assessment of melatonin's ability to regulate cytokine production by macrophage and microglia cell types.

Evidence in support of melatonin's role as an immunomodulator is incomplete and, in some cases, contradictory. The present studies determined whether melatonin modulates the activity of stimulated macrophages. In vitro lipopolysaccharide (LPS, 10-1000 ng/ml) treatment of alveolar, splenic and peritoneal macrophages isolated from mice and/or rats resulted in a dose-dependent increase in interleukin-1beta (IL-1beta) and tumor necrosis factor (TNF-alpha) secretion. Treatment with melatonin (10(-10)-10(-6) M) prior to the addition of LPS, had no effect on IL-1beta or TNF-alpha release. Additionally, melatonin had no effect on stimulated BV2 microglial cell line cytokine secretion. To determine whether melatonin had an indirect effect on macrophage cytokine release via T cells, melatonin was added to unfractionated mouse spleen cells. Again, melatonin showed no priming effect on LPS-stimulated spleen cells. These results suggest that melatonin has no direct or indirect effect on mouse and rat macrophages. In vivo studies, where melatonin was continuously available in the drinking water, showed that melatonin did not have a priming effect on LPS-stimulated mouse peritoneal macrophages. These findings suggest that melatonin is not an important modulator of macrophage and microglia function.