GRANULOCYTE-COLONY-STIMULATING FACTOR AND AZOLE ANTIFUNGAL THERAPY INMURINE ASPERGILLOSIS - ROLE OF IMMUNE SUPPRESSION

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