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Antimicrobial Agents and Chemotherapy, December 2000, p. 3328-3336, Vol. 44, No. 12
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

George S. Deepe Jr.* and Reta Gibbons

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.


* 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.


Antimicrobial Agents and Chemotherapy, December 2000, p. 3328-3336, Vol. 44, No. 12
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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