Antifungal activity of recombinant human macrophage colony-stimulating factor in models of acute and chronic candidiasis in the rat.
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.
Vitt
C R
CR
Department of Pharmacology, Chiron Corp., Emeryville, California 94608-2916.
Fidler
J M
JM
Ando
D
D
Zimmerman
R J
RJ
Aukerman
S L
SL
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
D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D015725:Fluconazole