Interleukin-12 protects mice against disseminated infection caused by Paracoccidioides brasiliensis but enhances pulmonary inflammation.
Paracoccidioides brasiliensis is a facultative, intracellular pathogen causing the most important deep mycosis in Latin America. As the production of IFN-gamma 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-gamma, 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.
Arruda
Celina
C
Departmento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil.
Franco
Marcello F
MF
Kashino
Suely S
SS
Nascimento
Flávia R F
FR
Fazioli
Raquel dos Anjos
Rdos A
Vaz
Celidéia A C
CA
Russo
Momtchilo
M
Calich
Vera L G
VL
D000818:Animals; D000908:Antibodies, Fungal / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D006801:Humans; D006968:Hypersensitivity, Delayed; D007167:Immunotherapy; D018664:Interleukin-12 / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D010228:Paracoccidioides / Q000276:immunology / Q000302:isolation & purification; D010229:Paracoccidioidomycosis / Q000209:etiology / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control
D000908:Antibodies, Fungal; D016207:Cytokines; D018664:Interleukin-12