Human Lymphocyte-Synthesized Melatonin Is Involved in the Regulation of the Interleukin-2/Interleukin-2 Receptor System

Abstract

Since melatonin was first isolated in 1958 up to the last few years, this substance was considered a hormone exclusive to the pineal gland. Although melatonin has lately been identified in a large number of extrapineal sites, its potential biological actions have not yet been studied. This paper shows that human lymphocyte-synthesized melatonin plays a crucial role modulating IL-2/IL-2 receptor system because when blocking melatonin biosynthesis by the tryptophan hydroxylase inhibitor, parachlorophenylalanine, both IL-2 and IL-2 receptor levels fell, restoring them by adding exogenous melatonin. Moreover, we demonstrated that this endogenous melatonin interfered with the exogenous melatonin effect on IL-2 production. Melatonin exerted these effects by a receptor-mediated action mechanism because both IL-2 and IL-2 receptor expressions significantly decreased when lymphocytes were incubated in the presence of the specific membrane and/or nuclear melatonin receptor antagonists, luzindole, and/or CGP 55644, respectively. Finally, we made the real significance of the membrane melatonin receptors in this process clear, so prostaglandin E(2)-induced inhibition on IL-2 production increased when we blocked the membrane receptors using luzindole. In conclusion, these data show that endogenous melatonin is an essential part for an accurate response of human lymphocytes through the modulation of IL-2/IL-2 receptor system.

Diurnal variation in phagocytic activity of splenic phagocytes in freshwater teleost Channa punctatus: melatonin and its signaling mechanism

“…However, experimental evidence implicating the role of melatonin in regulation of diurnal variation in phagocytosis is lacking. In the present study, administration of pCPA, an irreversible tryptophan hydroxylase inhibitor known to diminish melatonin biosynthesis (Carrillo-Vico et al 2005), completely abolished the decrease in phagocytosis observed during dark phase. The decreased melatonin level might be implicated for this effect though the serum melatonin was not measured in these spotted murrel fish.…”

“…pCPA is a known irreversible tryptophan hydroxylase inhibitor, and hence, diminishes the melatonin synthesis (Carrillo-Vico et al 2005). A single dose of pCPA (100 mg/kg body weight) in C. punctatus is reported to considerably reduce serotonin that is the precursor of melatonin, within 2 h of its administration.…”

International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors

“…In rat microvasculature, MT 2 activation also reduces acute inflammation by inhibiting leukocyte rolling (Lotufo et al, 2001). In human lymphocytes MT 1 receptor activation counteracts the inhibitory effect of prostaglandin E 2 on interleukin 2 production (Carrillo-Vico et al, 2003;Carrillo-Vico et al, 2005). Activation of MT 2 receptors modulates immune responses, providing a mechanism by which endogenous melatonin may participate in adaptation to seasonal changes (Table 1).…”

Melatonin Protects CD4+ T Cells from Activation-Induced Cell Death by Blocking NFAT-Mediated CD95 Ligand Upregulation

“…In particular, endogenous production of melatonin by human lymphocytes has been related to enhanced release of IL-2 and upregulation of IL-2R (20), suggesting that melatonin may be involved in the clonal expansion of Ag-stimulated human T lymphocytes. Importantly, the effects of melatonin on activated T cell death remain largely unknown.…”