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

Antimicrob Agents Chemother. 2000 Dec;44(12):3328-36. doi: 10.1128/AAC.44.12.3328-3336.2000.

Abstract

Several endogenous cytokines, including granulocyte-macrophage colony-stimulating factor (GM-CSF), are necessary for eliminating Histoplasma capsulatum from tissues. In this study, we explored the efficacy of recombinant murine GM-CSF in the treatment of pulmonary histoplasmosis. This cytokine significantly reduced fungal burden in a dose-dependent manner. Pretreatment did not consistently produce a better result than treatment started after infection. The biological effectiveness of GM-CSF was not associated with modulation of lung cytokine production or alteration in lung inflammation, but it directly activated a nonadherent lung cell population to exert anti-Histoplasma 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 adjunctive treatment for histoplasmosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amphotericin B / pharmacology
  • Animals
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Flow Cytometry
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Histoplasma / drug effects
  • Histoplasmosis / drug therapy*
  • Histoplasmosis / immunology
  • Histoplasmosis / physiopathology
  • Histoplasmosis / prevention & control
  • Immunocompetence
  • Immunocompromised Host
  • Leukocytes / metabolism
  • Lung / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Recombinant Proteins

Substances

  • Cytokines
  • Recombinant Proteins
  • Amphotericin B
  • Granulocyte-Macrophage Colony-Stimulating Factor