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

Individuals of many vertebrate species undergo seasonal changes in immune f unction in addition to marked seasonal changes in reproductive, metabolic, and other physiological processes. Despite growing evidence that photoperio d mediates seasonal changes in immunity, little is known regarding the neur oendocrine mechanisms underlying these changes. Enhanced immune function in short days is correlated with increased duration of nightly melatonin secr etion, and recent studies indicate that melatonin can act directly on immun e cells to enhance immune function. It remains unknown, however, which mela tonin receptor subtype mediates immune enhancement by melatonin. The presen t study examined the contribution of specific melatonin receptor subtypes, mt1 (Mel 1a) and MT2 (Mel 1b), in mediating melatonin-induced enhancement o f cell-mediated and humoral immune function in mice. Melatonin enhanced bot h splenocyte proliferation and anti-keyhole limpet hemocyanin (KLH) IgG con centrations in both wild-type WT) and mice lacking a functional gene for me latonin receptor mt1 (mt1 -/-), suggesting that the mt1 receptor does not m ediate these responses. In addition, luzindole, an MT2 receptor antagonist, attenuated melatonin-induced enhancement of splenocyte proliferation in bo th WT and mt1 -/- mice. Taken together, these results suggest that receptor subtype mt1 is not necessary for mediating melatonin-induced enhancement o f immune function and provide the first evidence for a specific melatonin r eceptor subtype, MT2, that may be involved in melatonin-induced immune enha ncement. Copyright (C) 2001 S. Karger AG, Basel.