Granulocyte colony-stimulating factor and azole antifungal therapy in murine aspergillosis: role of immune suppression.
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.
University of Texas Health Science Center San Antonio, San Antonio, Texas 78284, USA. GRAYBILL@UTHSCSA.EDU
J R
JR
Graybill
R
R
Bocanegra
L K
LK
Najvar
D
D
Loebenberg
M F
MF
Luther
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000627:therapeutic use*; D001228:Aspergillosis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D007165:Immunosuppression Therapy; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D014230:Triazoles / Q000627:therapeutic use*
D000305:Adrenal Cortex Hormones; D000935:Antifungal Agents; D014230:Triazoles; D016179:Granulocyte Colony-Stimulating Factor; C101425:posaconazole