Melatonin enhances pro-inflammatory cytokine levels and protects against Chagas disease.
Pro-inflammatory and modulatory cytokines have an essential role in host defense against human and murine Trypanosoma cruzi infection. Control of T. cruzi parasitism during the acute phase of infection is considered to be critically dependent on direct macrophage activation by cytokines. Melatonin has been proposed to regulate the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. The aims of this work were to evaluate in rats, the influences of exogenous melatonin treatment on T. cruzi-infected host's immune responses. With this in mind, several immunological parameters were analyzed, including tumor necrosis factor-alpha, gamma-interferon, interleukin-12, nitric oxide (NO) and macrophage count. The melatonin therapy was provided in one of two different treatment regimens, that is, either beginning 7 days prior to infection or concomitant with the infection. Both treatments triggered an up-regulation of the immune response, with the concomitant treatment being more effective; in this case all cytokines studied, with exception of NO, displayed enhanced concentrations and there was a higher number of peritoneal macrophages, which displayed reduced concentrations under melatonin therapy. We conclude that melatonin plays a pivotal role in up-regulating the Th1 immune response thus controlling parasite replication.
Santello
Fabricia Helena
FH
Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirao Preto, SP, Brazil. santello@fcfrp.usp.br
Frare
Eduardo Osório
EO
Caetano
Leony Cristina
LC
AlonsoToldo
Míriam Paula
MP
do Prado
José Clóvis
JC
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D014355:Chagas Disease / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology* / Q000627:therapeutic use; D007371:Interferon-gamma / Q000097:blood; D008297:Male; D008550:Melatonin / Q000502:physiology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017208:Rats, Wistar; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000276:immunology
D000981:Antiprotozoal Agents; D016207:Cytokines; D018836:Inflammation Mediators; D007371:Interferon-gamma; D008550:Melatonin