Interleukin-10 but not Transforming Growth Factor beta inhibits murine activated macrophages Paracoccidioides brasiliensis killing: effect on H2O2 and NO production.

Paracoccidioidomycosis is caused by the thermally dimorphic fungus Paracoccidioides brasiliensis (P. brasiliensis). Most often, this mycosis runs as a chronic progressive course affecting preferentially the lungs. In vitro fungicidal activity against a high virulent strain of P. brasiliensis by murine peritoneal macrophages preactivated with IFN-gamma or TNF-alpha is high and correlates with increased NO and H2O2 production. Within this context, the purpose of this work was to study the role of suppressor cytokines, such as IL-10 and TGF-beta, in this process. Incubation of either IFN-gamma or TNF-alpha with IL-10 inhibits fungicidal activity of these cells. However, TGF-beta had no effect on fungicidal activity of IFN-gamma or TNF-alpha-activated macrophages. The suppression of fungicidal activity by IL-10 correlated with the inhibition of NO and H2O2 production supporting the involvement of these metabolites in P. brasiliensis killing. These results suggest that IL-10 production in vivo could represent an evasion mechanism of the fungus to avoid host immune response.