Evidence for a Direct Action of Melatonin on the Immune System

Abstract

Pineal melatonin modulates the mammalian immune system. In vivo studies showed that melatonin enhanced the natural and acquired immunity while in vitro studies demonstrated its inhibitory influence. The mechanism of melatonin action on the immune system remains unknown. Actions through lymphokines or opioid release or via other endocrine changes have been proposed. In this paper, a direct action of melatonin on the lymphoid tissue is hypothesized. 2-[¹²⁵I]Iodomelatonin binding sites have been identified in the membrane homogenates of thymus, bursa of Fabricius and spleens of a number of birds and mammals. The bindings were stable, saturable, reversible, specific and of high affinity. The Bmax ranged from 0.6 to 3.9 fmol/mg protein. The Kd was in the physiological range of circulating melatonin levels, about 30–70 pmol/l. The binding sites in the primary lymphoid organs demonstrated diurnal variation in density, with higher levels found at the middle of the light period. However, those in the spleen did not vary with the time of the day. An age-dependent decrease in the density was also found in the chicken bursa of Fabricius. In addition, when the noctural melatonin secretion was suppressed by constant light exposure, the density of the binding sites increased in the guinea pig spleen. Immunosuppression with Cortisol injection in young ducks decreased the density of the melatonin binding sites in the thymus. The regulation of the binding characteristics by physiological variation in melatonin levels and/or immunological status of the animals provide evidence that these 2-[¹²⁵I]iodomelatonin binding sites in the lymphoid tissues may be physiologically significant and represent true melatonin receptors. The melatonin receptors in the lymphoid organs may be coupled to a G protein as Guanosine 5''-O-(3-thiotri-phosphate inhibited 2-[¹²⁵I]iodomelatonin binding in the spleen by increasing the Kd and decreasing the Bmax.

The melatonin immunomodulatory actions in radiotherapy

“…These results suggest that melatonin enhances the anti-tumor function of NK cells. Although the exact mechanisms of the stimulatory effect of melatonin on NK cells have not been completely defined, increasing IL-2 production through the stimulation of T cell melatonin receptors has been proposed (Poon et al 1994;Christopher et al 1991). In a study on tumor model mice, daily administration of melatonin resulted in a 2.5-fold increase in NK cell number at 9 days.…”

Melatonin-Induced Oncostasis, Mechanisms and Clinical Relevance

“…Melatonin administration to leukemic mice results in a quantitative and functional enhancement of NK cells [74]. Although the mechanism has not been defined directly, one possibility is that melatonin acts through increased IL-2 production via melatonin receptors in T-helper cells [75], which leads to an increase in NK cell number and function [76]. T-helper cells play a crucial role in protection against malignancy.…”

Therapeutic Actions of Melatonin in Cancer: Possible Mechanisms

“…Because NK cells are effective against a variety of tumors, especially leukemias and lymphomas, the regulation of NK cell activity and the enhancement of the cytolytic function of NK cells by melatonin 152 have considerable significance for possible therapeutic applications.…”