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Control of the acute phase of Trypanosoma cruzi infection is critically dependent on cytokine-mediated macrophage activation to intracellular killing, natural killer (NK) cells, CD4+ T cells, CD8+ T cells and B cells. Cell-mediated immunity in T. cruzi infection is also modulated by cytokines, but in addition to parasite-specific responses, autoimmunity can be also triggered. Importantly, cytokines may also play a role in the cell-mediated immunity of infected subjects. Here we studied the role of cytokines in the regulation of innate and adaptive immunity during the acute phase of T. cruzi infection in Wistar rats. Melatonin is an effective regulator of the immune system. Macrophages and T lymphocytes, which have melatonin receptors, are target cells for the immunomodulatory function of melatonin. In this paper melatonin was orally given via two protocols: prior to and concomitant with infection. Both treatments were highly effective against T. cruzi with enhanced action for the concomitant treatment. The data suggest an up-regulation of the TH-1 immune response as all analyzed parameters, interleukin (IL)-4, IL-10, transforming growth factor-β1 and splenocyte proliferation, displayed reduced levels as compared with the untreated counterparts. However, the direct effects of melatonin on immune cells have not been fully investigated during T. cruzi infection. We conclude that in light of the current results, melatonin exerted important therapeutic benefits through its immune regulatory effects. [ABSTRACT FROM AUTHOR]

Melatonin affects a variety of physiological processes including circadian rhythms, cellular redox status, and immune function. Importantly, melatonin significantly influences T-cell-mediated immune responses, which are crucial to protect mammals against cancers and infections, but are associated with pathogenesis of many autoimmune diseases. This review focuses on our current understanding of the significance of melatonin in T-cell biology and the beneficial effects of melatonin in T-cell response-based diseases. In addition to expressing both membrane and nuclear receptors for melatonin, T cells have the four enzymes required for the synthesis of melatonin and produce high levels of melatonin. Meanwhile, melatonin is highly effective in modulating T-cell activation and differentiation, especially for Th17 and Treg cells, and also memory T cells. Mechanistically, the influence of melatonin in T-cell biology is associated with membrane and nuclear receptors as well as receptor-independent pathways, for example, via calcineurin. Several cell signaling pathways, including ERK1/2-C/ EBPα, are involved in the regulatory roles of melatonin in T-cell biology. Through modulation in T-cell responses, melatonin exerts beneficial effects in various inflammatory diseases, such as type 1 diabetes, systemic lupus erythematosus, and multiple sclerosis. These findings highlight the importance of melatonin signaling in T-cell fate determination, and T cell-based immune pathologies. [ABSTRACT FROM AUTHOR]