Efficacy of interferon-gamma and amphotericin B for the treatment of systemic murine histoplasmosis

The number of cases of systemic histoplasmosis has increased substantially in recent years, and improved therapy is needed. We examined the efficacy o f immunomodulation with interferon (IFN)-gamma alone or in combination with a suboptimal regimen of amphotericin B for the treatment of primary system ic murine histoplasmosis. In the first study, BALB/c mice were infected wit h Histoplasma capsulatum G217B and treated with 10(5) U of IFN given every other day either preinfection and postinfection or only postinfection, alon e or in combination with amphotericin B. IFN alone given subcutaneously (s. c.) postinfection prolonged survival over untreated controls (P < 0.01), wh ereas intravenous (i.v.) administration was ineffective. All combination re gimens and amphotericin B alone significantly prolonged survival (P < 0.000 1). The combination regimens of amphotericin B and IFN i.v. (pre- and posti nfection) or IFN s.c. (postinfection) reduced the fungal burden in the live r and spleen; the latter regimen had superior efficacy in the spleen (P < 0 .05) to either amphotericin B or IFN alone. After infection with a low-chal lenge inoculum, IFN given s.c. (pre- and postinfection) alone caused a sign ificant reduction in fungal burden in the spleen (P < 0.001). In an acutely lethal model, combination regimens of IFN s.c. or i.v. and amphotericin B again prolonged survival (P < 0.01-0.001), with amphotericin B plus IFN giv en s.c. (pre- and postinfection) superior to all regimens (P < 0.05-0.01). This regimen also showed enhanced efficacy in causing the reduction of fung al burden in the spleen (P < 0.05). These results indicate that IFN in comb ination with AmB shows enhanced efficacy in the treatment of systemic histo plasmosis and support the potential utility of IFN as an adjunctive therapy . (C) 2001 Editions scientifiques et medicales Elsevier SAS.