Singh Nina, Heitman Joseph
University of Pittsburgh Medical Center, Thomas E. Starzl Transplantation Institute, Pittsburgh, PA, USA. nis5+@pitt.edu
Transplantation. 2004 Mar 27;77(6):795-800. doi: 10.1097/01.tp.0000117252.75651.d6.
The currently available immunosuppressive agents cyclosporine A, tacrolimus, and rapamycin have potent antifungal activity against a number of opportunistic fungi in organ transplant recipients, most notably, C. neoformans, Candida, and Aspergillus species. The targets of their antifungal activity are fungal homologs of the signaling molecules that mediate their immunosuppressive action in humans, which has implications for further unraveling the pathogenesis of these infections. Corroborative clinical data suggest that despite the apparent paradox between the antifungal activity of the immunosuppressive agents and the occurrence of fungal infections during their administration, the antifungal attributes of these drugs may influence the spectrum and clinical characteristics of these infections after organ transplantation. Finally, the potent synergistic interactions between the immunosuppressive agents and antifungal drugs against many pathogenic fungi, including those that are typically resistant to traditional antifungal agents, could potentially have a role in devising novel therapeutic strategies for opportunistic mycoses in transplant recipients.
目前可用的免疫抑制剂环孢素A、他克莫司和雷帕霉素对器官移植受者中的多种机会性真菌具有强大的抗真菌活性，最显著的是新生隐球菌、念珠菌和曲霉菌种。它们抗真菌活性的靶点是在人类中介导其免疫抑制作用的信号分子的真菌同源物，这对于进一步阐明这些感染的发病机制具有重要意义。确凿的临床数据表明，尽管免疫抑制剂的抗真菌活性与给药期间真菌感染的发生之间存在明显矛盾，但这些药物的抗真菌特性可能会影响器官移植后这些感染的范围和临床特征。最后，免疫抑制剂与抗真菌药物对许多致病真菌，包括那些通常对传统抗真菌药物耐药的真菌之间的强大协同相互作用，可能在为移植受者的机会性真菌病设计新的治疗策略方面发挥作用。
