シクロスポリンA、タクロリムス（FK506）、またはシロリムス（ラパマイシン）に免疫抑制されたマウスの侵襲性アスペルギル症

シクロスポリンA、タクロリムス、およびシロリムスは、最初はアスペルギルス種の異なる活性を持つ抗真菌性化合物と呼ばれる免疫抑制剤です。各薬剤で治療されたマウスにおける侵襲性アスペルギル症の結果を、異化したCD-1マウスで調査しました。免疫抑制剤またはビヒクルのみを-1〜 +14に投与しました。マウスを0日目に、横方向の尾静脈注射を介してアスペルギルス分生子を安静時に感染させた。生存率は、シクロスポリンA（100 mg/kg/日、生存期間中央値、3日）で処理したマウスよりもほとんどのレジメンで有意に大きかった：タクロリムス、1 mg/kg/日（6.5日、p = .003）;シロリムス、1または10 mg/kg/日（それぞれ7.5および9.5日; p = .002および.0001）;車両だけ（6.5日、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.

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 cyclosporin 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.