Suppressive action of melatonin on the TH-2 immune response in rats infected with Trypanosoma cruzi.
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-beta1 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.
Santello
Fabricia Helena
FH
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Brasil. santello@fcfrp.usp.br
Frare
Eduardo Osório
EO
dos Santos
Carla Domingues
CD
Caetano
Leony Cristina
LC
Alonso Toldo
Míriam Paula
MP
do Prado
José Clóvis
JC
D000704:Analysis of Variance; D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy / Q000276:immunology* / Q000469:parasitology; D003208:Concanavalin A / Q000494:pharmacology; D016207:Cytokines / Q000097:blood*; D007110:Immunity, Active; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008264:Macrophages / Q000276:immunology; D008550:Melatonin / Q000008:administration & dosage / Q000494:pharmacology*; D018512:Parasitemia; D051381:Rats; D017208:Rats, Wistar; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood; D014349:Trypanosoma cruzi / Q000502:physiology
D016207:Cytokines; D016212:Transforming Growth Factor beta; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; D008550:Melatonin