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The role of IL-12 in experimental Trypanosoma cruzi infection
Braz. j. med. biol. res ; 31(1): 111-5, Jan. 1998.
Article in English | LILACS | ID: lil-212545
ABSTRACT
Host resistance to Trypanosoma cruzi infection in dependent on both natural and acquired immune responses. During the early acute phase of infection in mice, natural killer (NK) cell-derived IFN-gamma is involved in controlling intracellular parasite replication, mainly through the induction of nitric oxide biosynthesis by activate macrophages. We have shown that IL-12, a powerful inducer of IFN-gamma production by NK cells, is synthesized soon after trypomastigote-macrophage interaction. The role of IL-12 in the control of T. cruzi infection in vivo was determined by treating infected mice with anti-IL-12 monoclonal antibody (mAb) and analyzing both parasitemia and mortality during the acute phase of infection. The anti-IL-12 mAb-treated mice had higher levels of parasitemia and mortality compared to control mice. Also, treatment of infected mice with mAb spectific for IFN-gamma or TNF-alpha inhibited the protective effect of exogenous IL-12. On the other hand, TGF-beta and IL-10 produced by infected macrophages inhibited the induction and effects of IL-12. Therefore, while IL-12, TNF-alpha and IFN-gamma correlate with resistance to T. cruzi infection, TGF-beta and IL-10 promote susceptibility. These results provide support for a role of innate immunity in the control of T. cruzi infection. In addition to its protective role, IL-12 may also be involved in the modulation of T. cruzi-induced myocarditis, since treatment of infected mice with IL-12 or anti-IL-12 mAb leads to an enhanced or decreased inflammatory infiltrate in the heart, respectively. Understanding the role of the cytokine produced during the acute phase of T. cruzi infection and their involvement in protection and pathogenesis would be essential to devise new vaccines or therapies.
Subject(s)
Full text: Available Index: LILACS (Americas) Main subject: Trypanosoma cruzi / Trypanosomiasis / Interleukin-12 / Disease Models, Animal Type of study: Prognostic study Limits: Animals Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 1998 Type: Article / Congress and conference

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Full text: Available Index: LILACS (Americas) Main subject: Trypanosoma cruzi / Trypanosomiasis / Interleukin-12 / Disease Models, Animal Type of study: Prognostic study Limits: Animals Language: English Journal: Braz. j. med. biol. res Journal subject: Biology / Medicine Year: 1998 Type: Article / Congress and conference