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Antimicrobial Agents and Chemotherapy, December 2000, p. 3328-3336, Vol. 44, No. 12
Division of Infectious Diseases, University
of Cincinnati College of Medicine and the Veterans Affairs
Hospital, Cincinnati, Ohio
Received 7 June 2000/Returned for modification 30 August
2000/Accepted 25 September 2000
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.
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Recombinant Murine Granulocyte-Macrophage Colony-Stimulating
Factor Modulates the Course of Pulmonary Histoplasmosis in
Immunocompetent and Immunodeficient Mice
*
Corresponding author. Mailing address: Division of
Infectious Diseases, University of Cincinnati College of Medicine, 231 Bethesda Ave., Cincinnati, OH 45267-0560. Phone: (513) 558-4704. Fax:
(513) 558-2089. E-mail: george.deepe{at}uc.edu.
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