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Interleukin-12 Protects Mice against Disseminated Infection Caused by Paracoccidioides brasiliensis but Enhances Pulmonary Inflammation

2002; Elsevier BV; Volume: 103; Issue: 2 Linguagem: Inglês

10.1006/clim.2002.5207

1521-7035

Celina Arruda, Marcello Fabiano de Franco, Suely Sanae Kashino, Flávia Raquel Fernandes do Nascimento, Raquel dos Anjos Fazioli, Celidéia Aparecida Coppi Vaz, Momtchilo Russo, Vera Lúcia Garcia Calich,

Toxin Mechanisms and Immunotoxins

Paracoccidioides brasiliensis is a facultative, intracellular pathogen causing the most important deep mycosis in Latin America. As the production of IFN-γ and induction of cell-mediated immunity to P. brasiliensis is of critical importance in host defense, the immunotherapeutic effect of exogenous IL-12 administration was studied in a murine model of susceptibility to pulmonary infection. rIL-12 treatment led to a less disseminated disease, as confirmed by decreased fungal loads in liver and spleen. Administration of rIL-12 did not affect fungal growth in the lungs, although it did induce an augmented pulmonary mononuclear cell inflammation. IL-12 treatment induced an early (week 1) increase in pulmonary IFN-γ, but decreased cytokine and specific antibody (IgG1 and IgG3) production at week 8 after infection. These results show that IL-12 administration induces a less severe infection, but the high inflammatory response detected in the lungs precludes its possible use as a new therapeutic tool for severe paracoccidioidomycosis.