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-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.
Deepe
G S
GS
Division of Infectious Diseases, University of Cincinnati College of Medicine and the Veterans Affairs Hospital, Cincinnati, Ohio 45267-0560, USA. george.deepe@uc.edu
Gibbons
R
R
D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D006658:Histoplasma / Q000187:drug effects; D006660:Histoplasmosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control; D007121:Immunocompetence; D016867:Immunocompromised Host; D007962:Leukocytes / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins
D016207:Cytokines; D011994:Recombinant Proteins; D000666:Amphotericin B; D016178:Granulocyte-Macrophage Colony-Stimulating Factor