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Antimicrobial Agents and Chemotherapy, October 1998, p. 2467-2473, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Granulocyte Colony-Stimulating Factor and Azole Antifungal Therapy in Murine Aspergillosis: Role of Immune Suppression

John R. Graybill,1,2,* Rosie Bocanegra,1 Laura K. Najvar,1 David Loebenberg,3 and Mike F. Luther2

University of Texas Health Science Center San Antonio1 and Audie Murphy Veterans Administration Hospital,2 San Antonio, Texas, and Schering-Plough, Research Institute, Kenilworth, New Jersey3

Received 2 February 1998/Returned for modification 25 March 1998/Accepted 10 June 1998

Outbred ICR mice were immune suppressed either with hydrocortisone or with 5-fluorouracil and were infected intranasally with Aspergillus fumigatus. Beginning 3 days before infection some groups of mice were given recombinant human granulocyte colony-stimulating factor (G-CSF), SCH56592 (an antifungal triazole), or both. Corticosteroid-pretreated mice responded to SCH56592 and had reduced counts in lung tissue and prolonged survival. In these mice, G-CSF strongly antagonized the antifungal activity of SCH56592. Animals treated with both agents developed large lung abscesses with polymorphonuclear leukocytes and large amounts of Aspergillus. In contrast, mice made neutropenic with 5-fluorouracil and then infected with A. fumigatus conidia benefited from either G-CSF or triazoles, and the effect of the combination was additive rather than antagonistic. Host predisposing factors contribute in different ways to the outcome of growth factor therapy in aspergillosis.

* Corresponding author. Mailing address: Infectious Diseases Section (111F), Audie L. Murphy Memorial Veterans Hospital, 7400 Merton Minter Blvd., San Antonio, TX 78284. Phone: (210) 617-5111. Fax: (210) 614-6197. E-mail: GRAYBILL{at}UTHSCSA.EDU.

Antimicrobial Agents and Chemotherapy, October 1998, p. 2467-2473, Vol. 42, No. 10
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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