Melatonin receptor subtype MT2 (Mel 1b) and not mt1 (Mel 1a) is associated with melatonin-induced enhancement of cell-mediated and humoral immunity.

Individuals of many vertebrate species undergo seasonal changes in immune function in addition to marked seasonal changes in reproductive, metabolic, and other physiological processes. Despite growing evidence that photoperiod mediates seasonal changes in immunity, little is known regarding the neuroendocrine mechanisms underlying these changes. Enhanced immune function in short days is correlated with increased duration of nightly melatonin secretion, and recent studies indicate that melatonin can act directly on immune cells to enhance immune function. It remains unknown, however, which melatonin receptor subtype mediates immune enhancement by melatonin. The present study examined the contribution of specific melatonin receptor subtypes, mt1 (Mel 1a) and MT2 (Mel 1b), in mediating melatonin-induced enhancement of cell-mediated and humoral immune function in mice. Melatonin enhanced both splenocyte proliferation and anti-keyhole limpet hemocyanin (KLH) IgG concentrations in both wild-type (WT) and mice lacking a functional gene for melatonin receptor mt1 (mt1 -/-), suggesting that the mt1 receptor does not mediate these responses. In addition, luzindole, an MT2 receptor antagonist, attenuated melatonin-induced enhancement of splenocyte proliferation in both WT and mt1 -/- mice. Taken together, these results suggest that receptor subtype mt1 is not necessary for mediating melatonin-induced enhancement of immune function and provide the first evidence for a specific melatonin receptor subtype, MT2, that may be involved in melatonin-induced immune enhancement.