Mechanisms of interaction between melatonin with lymphocytes

Melatonin is an indoleamine synthesized from the essential amino acid tryptophan. At the system level, it is produced mainly by the pineal gland, and at the local level, by most organs and tissues, including the gastrointestinal tract, liver, kidneys, lungs, skin, tissues of the reproductive system, and many others. The hormone regulates a wide range of biological reactions in health and diseases, and has a pronounced antioxidant, anti-inflammatory and antitumor activity. Along with this, melatonin is an effective regulator of the immune system, however, the data available to date on the problem are extremely contradictory, especially for the main effectors of adaptive immunity - T-lymphocytes. On the one hand, under physiological conditions or under immunodeficiency conditions, the effects of melatonin are usually stimulatory: it enhances the proliferative response of T- and B-lymphocytes, increases the production of Th1-cytokines, and inhibits apoptosis of lymphocytes induced by various stimuli. On the other hand, there are no fewer works demonstrating the immunosuppressive activity of melatonin, in particular, suppression of the production of pro-inflammatory cytokines. The resolution of these contradictions is the goal of this review. At the same time, the work focuses on two fundamental points. First, the main part of immunostimulating effects was obtained in experiments in vitro, while immunosuppressive effects were obtained in vivo, and since melatonin controls the synthesis of a number of other hormones of the hypothalamic-pituitary-adrenal and / or gonadal axes, many of which are effective immuno-modulators themselves, it direct effects in vivo can be mediated and offset by other hormones. Second, lymphocytes express three high-affinity melatonin receptors: two membrane receptors, MT1 and MT2, and a nuclear one, RORα, as well as a number of low-specific targets, all with varying affinities for melatonin. Binding of different receptors apparently triggers different signaling mechanisms. Accordingly, physiological, pathological and pharmacological concentrations of melatonin can have different immunomodulating effects, and when evaluating the effect of melatonin on the immune system, it is important to correlate the hormone concentrations with the state of the receptor apparatus of the cells under study.