Recombinant murine granulocyte-macrophage colony-stimulating factor modulates the course of pulmonary histoplasmosis in immunocompetent and immunodeficient mice

Several endogenous cytokines, including granulocyte-macrophage colony-stimu lating factor (GM-CSF), are necessary for eliminating Histoplasma capsulatu m from tissues. In this study, we explored the efficacy of recombinant muri ne GM-CSF in the treatment of pulmonary histoplasmosis. This cytokine signi ficantly reduced fun gal burden in a dose-dependent manner. Pretreatment di d not consistently produce a better result than treat ment started after in fection. The biological effectiveness of GM-CSF was not associated with mod ulation of lung cytokine production or alteration in lung inflammation, but it directly activated a nonadherent lung cell population to exert anti-His toplasma activity. GM-CSF improved survival of T-cell depleted mice exposed to H. capsulatum, When combined with a suboptimal amount of amphotericin B , GM-CSF enhanced survival of normal or T-cell-depleted mice given a lethal challenge. These results suggest that this cytokine may be useful as an ad junctive treatment for histoplasmosis.