Invasive aspergillosis in mice immunosuppressed with cyclosporin A, tacrolimus (FK506), or sirolimus (rapamycin)

High, K. P.;Washburn, R. G.

Author address: 

High, KP, WAKE FOREST UNIV,BOWMAN GRAY SCH MED,DEPT INTERNAL MED,INFECT DIS SECT,BGSM,100 MED CTR BLVD,WINSTON SALEM,NC 27157

Abstract: 

Cyclosporin A, tacrolimus, and sirolimus are immunosuppressive agents initially described as antifungal compounds with different activities for Aspergillus species. The outcome of invasive aspergillosis in mice treated with each agent was investigated in outbred CD-1 mice. Immunosuppressant or vehicle alone was administered from days -1 to +14. Mice were infected on day 0 with resting Aspergillus conidia via lateral tail vein injection. Survival was significantly greater with most regimens than for mice treated with cyslosporin A (100 mg/kg/day; median survival, 3 days): tacrolimus, 1 mg/kg/day (6.5 days, P = .003); sirolimus, 1 or 10 mg/kg/day (7.5 and 9.5 days, respectively; P = .002 and .0001); and vehicle alone (6.5 days, P = .001), However, mice treated with 10 mg/kg/day of tacrolimus survived a median of 4.5 days (P = .25), Survival in the 10-mg sirolimus group did not differ from that of mice given vehicle alone (P = .55), Histologic evaluation suggested the improved survival with tacrolimus and sirolimus may be due in part to direct anti-Aspergillus activity.
1995

abstract No: 

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Full conference title: 

35th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC)
    • ICAAC 35th