Melatonin enhancement of splenocyte proliferation is attenuated by luzindole, a melatonin receptor antagonist

In addition to marked seasonal changes in reproductive, metabolic, and othe r physiological functions, many vertebrate species undergo seasonal changes in immune function. Despite growing evidence that photoperiod mediates sea sonal changes in immune function, little is known regarding the neuroendocr ine mechanisms underlying these changes. Increased immunity in short days i s hypothesized to be due to the increase in the duration of nightly melaton in secretion, and recent studies indicate that melatonin acts directly on i mmune cells to enhance immune parameters. The present study examined the co ntribution of melatonin receptors in mediating the enhancement of splenocyt e proliferation in response to the T cell mitogen Concanavalin A in mice. T he administration of luzindole, a high-affinity melatonin receptor antagoni st, either in vitro or in vivo significantly attenuated the ability of in v itro melatonin to enhance splenic lymphocyte proliferation during the day o r night. In the absence of melatonin or luzindole, splenocyte proliferation was intrinsically higher during the night than during the day. In the abse nce of melatonin dministration, luzindole reduced the ability of spleen cel ls to proliferate during the night, when endogenous melatonin concentration s are naturally high. This effect was not observed during the day, when mel atonin concentrations are low. Taken together, these results suggest that m elatonin enhancement of splenocyte proliferation is mediated directly by me latonin receptors on splenocytes and that there is diurnal variation in spl enocyte proliferation in mice that is also mediated by splenic melatonin re ceptors.