Systemic candidiasis in mice treated with prednisolone and amphotericin B. 1. Morbidity, mortality and inflammatory reaction

Abstract

Prednisolone potentiated candidiasis in mice when given as dosages of 1 mg, s.c. at-1 and + 24 h in relation to the time of inoculation, i.p. with any of 4 isolates of C. albicans which differed in degree of pathogenicity. Enhancement was shown by increased intra-abdominal colonisation, haematogenous dissemination and percentage mortality. There was at least a seven-fold increase in the mean area occupied by fungal colonies in median, longitudinal sections of kidneys after prednisolone treatment. Compared with those of fungal controls, renal lesions were deficient in inflammatory cells, only a few polymorphonuclear leukocytes occurring peripherally. Amphotericin B (AmB) at a non-toxic, total dosage of 0.5 mg given in two injections of 0.25 mg, i.p. at intervals of 24 h rendered infections non-lethal, or significantly reduced their severity, when started 24 or 48 h after inoculation. When antifungal treatment was delayed until 72 h, however, early deaths occurred despite the fact that the mean renal section area occupied by pseudomycelium was little more than that of controls and fibrosis of lesions was characteristic. Early mortalities increased even further when AmB, commencing at 72 h, was combined with prednisolone. This effect was thought to be due to the release of some toxic factor(s) following the leaching of cells by AmB combined with depleted antibody levels. Ascitic fluids from infected mice given Ehrlich ascites tumour cells showed marked increases in the concentrations of alpha2 and gamma globulins. Concentrations were almost reduced to normal levels in animals treated with prednisolone and/or AmB.