Interaction of chemotherapy and immune defenses in experimental murine cryptococcosis.

Abstract

Congenitally athymic nude (nu/nu) and thymus-containing heterozygous (nu/X) mice were infected intraperitoneally with Cryptococcus neoformans over a wide range of challenge doses. Cryptococcal disease progressed more rapidly in nude mice than in their nu/X littermates. When nu/X mice were treated with amphotericin B, all survived an otherwise lethal dose of C. neoformans. At larger challenge doses, survival was prolonged in nu/nu mice treated with amphotericin B, but they later succumbed to cryptococcosis. At lower challenge doses, amphotericin B was curative in some nude mice. Therapy of nude mice with both amphotericin B and flucytosine further prolonged survival at high-dose challenge and increased the number of cures at low-dose challenge. These studies support an interaction of antifungal chemotherapy with thymus-dependent immune defense mechanisms. This interaction is most evident at high challenge doses, where antifungal chemotherapy cures nu/X mice but only modestly prolongs survival in nude mice.

• Authors: J R Graybill, P C Craven, L F Mitchell, D J Drutz
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 14 Issue 5 Pg. 659-67 (Nov 1978) ISSN: 0066-4804 [Print] United States
• PMID: 365086 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Amphotericin B
• Flucytosine

Topics

• Amphotericin B (blood, therapeutic use)
• Animals
• Cryptococcosis (drug therapy, immunology, microbiology)
• Cryptococcus neoformans (drug effects)
• Female
• Flucytosine (blood, therapeutic use)
• Immunity, Cellular (drug effects)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microbial Sensitivity Tests