title: Antifungal activity of recombinant human macrophage colony-stimulating factor in models of acute and chronic candidiasis in the rat.
abstract: Models of acute and chronic candidiasis were developed in Fischer 344 rats to evaluate the therapeutic efficacy of recombinant human macrophage colony-stimulating factor (rhM-CSF) alone and in combination with the antifungal agent fluconazole. In the acute model, rats were challenged by intravenous injection with 2 x 10(6) Candida albicans, approximately 4 times the LD50. Daily subcutaneous (sc) bolus injections of rhM-CSF for 10 days plus a single sc bolus dose of 0.3 mg/kg of fluconazole improved the median survival time from 5 days (32% survival) with fluconazole alone to > 30 days (88% survival) in the rhM-CSF- and fluconazole-treated rats. In the chronic model, daily sc bolus injections of rhM-CSF for 10 days plus a single sc bolus dose of 1.0 mg/kg of fluconazole decreased the median titer of C. albicans cultured from the kidneys by 10-fold at 15 and 30 days after infection. These studies showed that rhM-CSF treatment improved the therapeutic outcome in both the acute and chronic rat model of candidiasis when used with fluconazole, a standard fungistatic agent.
authors.affiliation: Department of Pharmacology, Chiron Corp., Emeryville, California 94608-2916.
authors.forename: C R
authors.initials: CR
authors.lastname: Vitt
authors.forename: J M
authors.initials: JM
authors.lastname: Fidler
authors.forename: D
authors.initials: D
authors.lastname: Ando
authors.forename: R J
authors.initials: RJ
authors.lastname: Zimmerman
authors.forename: S L
authors.initials: SL
authors.lastname: Aukerman
mesh_terms: D000208:Acute Disease; D000818:Animals; D002177:Candidiasis / Q000188:drug therapy*; D002908:Chronic Disease; D015725:Fluconazole / Q000627:therapeutic use; D007958:Leukocyte Count / Q000187:drug effects; D016173:Macrophage Colony-Stimulating Factor / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins
chemical_list: D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D015725:Fluconazole