Effect of Cyclophosphamide on Histoplasma capsulatum Infections in Mice

ABSTRACT

Mice were injected intraperitoneally (i.p.) with 300 mg of cyclophosphamide (CY)/kg of body weight, and 24 h later were injected i.p. with varying dosages of yeast-phase cells of Histoplasma capsulatum. At specific time intervals organs were removed, ground, and cultured to determine the number of viable organisms contained in the spleen, liver, and lungs. Injection of mice with CY was found to cause a dramatic increase in the numbers of parasites isolated from these organs when compared with non-drug-treated controls. Mice given 10⁷ yeast cells showed the largest increase in colony numbers. A greater than fivefold increase in the numbers of organisms isolated from the spleens of CY and 10³ yeast cell-treated mice, as compared with non-drug-treated animals, was observed at all time periods. The general trend for infected control animals was a decrease in colony numbers. All mice given CY plus 10⁷ yeast cells intravenously (i.v.) died by day 20 postinfection. Mice given CY and 10⁷ yeast cells i.p. showed no evidence of fatal Histoplasma infection. Deaths occurring by day 5 in CY-treated animals injected with H. capsulatum yeast cells i.v. or i.p. were considered due to bacterial infection or toxicity, or both. Hepatosplenomegaly was observed in mice treated with CY and 10⁷ yeast cells of H. capsulatum. Enlarged lungs were also noted. CY control mouse spleens weighed 30% less than normal spleens. Organs of animals injected with H. capsulatum alone did not vary significantly from those of normal mice. Complete drug-induced suppression of humoral antibody response was achieved for 10 days, as determined by hemagglutination titrations.