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

Abstract

In addition to marked seasonal changes in reproductive, metabolic, and other physiological functions, many vertebrate species undergo seasonal changes in immune function. Despite growing evidence that photoperiod mediates seasonal changes in immune function, little is known regarding the neuroendocrine mechanisms underlying these changes. Increased immunity in short days is hypothesized to be due to the increase in the duration of nightly melatonin secretion, and recent studies indicate that melatonin acts directly on immune cells to enhance immune parameters. The present study examined the contribution of melatonin receptors in mediating the enhancement of splenocyte proliferation in response to the T cell mitogen Concanavalin A in mice. The administration of luzindole, a high-affinity melatonin receptor antagonist, either in vitro or in vivo significantly attenuated the ability of in vitro melatonin to enhance splenic lymphocyte proliferation during the day or night. In the absence of melatonin or luzindole, splenocyte proliferation was intrinsically higher during the night than during the day. In the absence of melatonin administration, luzindole reduced the ability of spleen cells to proliferate during the night, when endogenous melatonin concentrations are naturally high. This effect was not observed during the day, when melatonin concentrations are low. Taken together, these results suggest that melatonin enhancement of splenocyte proliferation is mediated directly by melatonin receptors on splenocytes and that there is diurnal variation in splenocyte proliferation in mice that is also mediated by splenic melatonin receptors.

Blocking of melatonin synthesis and MT1 receptor impairs the activation of Jurkat T cells

“…The choice of MT 1 and not MT 2 was based in the fact that the majority of MLT effects described for lymphocytes seem to be mediated through this receptor subtype [28]. However, some evidence shows that MLT-induced enhancement of immune function is also mediated via MT 2 receptors, as Drazen et al have shown about splenocyte proliferation in mice [29,30].…”

Expression of membrane and nuclear melatonin receptor mRNA and protein in the mouse immune system

“…As an immunomodulator, melatonin has been reported to enhance cell-mediated and humoral immunity via its MT 2 receptor [52]. Moreover, administration of luzindole, a high-affinity melatonin membrane receptor antagonist, has been shown to attenuate the ability of melatonin to enhance splenic lymphocyte proliferation [53] and suppress experimental autoimmune encephalomyelitis [54]. Antiproliferative effects of melatonin have also been shown in LNCaP human prostate and murine colonic cancer through its MT 1 and RZR/ROR receptors, respectively [55,56].…”

Melatonin: A pleiotropic molecule regulating inflammation

“…Here the artificial shortening of day lengths or alternatively melatonin injections induce an increase in thymus weight [49] and spleen hypertrophy [50], implying a melatonin-mediated photoperiodic effect on the immune system. Furthermore, it was demonstrated that melatonin controls diurnal and seasonal rhythms of leukocyte proliferation [51], of cytokine production [44,45] and NK cell activity [52] in mammalian bone marrow cells. In other studies, the nocturnal peak of melatonin was associated with the proliferation peak of granulocytes and macrophage progenitor cells in mice [53].…”