Louie A, Baltch A L, Smith R P, Franke M A, Ritz W J, Singh J K, Gordon M A
Infectious Disease Section, Stratton VA Medical Center, Albany, New York.
J Infect Dis. 1995 Feb;171(2):406-15. doi: 10.1093/infdis/171.2.406.
In systemic candidiasis, endogenously produced tumor necrosis factor (TNF)-alpha prolongs survival of the infected host. To determine whether endogenously produced TNF-alpha has a beneficial effect beyond that provided by antifungal therapy, survival was assessed in infected mice that received fluconazole or amphotericin B alone and in combination with anti-TNF-alpha antibody. Neutralization of serum TNF-alpha did not affect survival in fluconazole recipients; however, for amphotericin B recipients, it significantly shortened mean survival. For both fluconazole and amphotericin B recipients, colony counts in organs were significantly higher in animals that also received anti-TNF-alpha antibody. Administration of anti-TNF-alpha antibody with amphotericin B or fluconazole did not affect the morphology of fungi or the inflammatory response in kidneys. This study suggests that exogenous TNF-alpha and drugs that increase the endogenous production of TNF-alpha by the host may be useful adjuncts to fluconazole and amphotericin B for the treatment of systemic candidiasis.
在系统性念珠菌病中，内源性产生的肿瘤坏死因子（TNF）-α可延长受感染宿主的存活时间。为了确定内源性产生的TNF-α是否具有超出抗真菌治疗的有益作用，我们评估了单独接受氟康唑或两性霉素B以及联合抗TNF-α抗体的感染小鼠的存活率。血清TNF-α的中和作用并未影响接受氟康唑治疗小鼠的存活率；然而，对于接受两性霉素B治疗的小鼠，它显著缩短了平均存活时间。对于接受氟康唑和两性霉素B治疗的小鼠，同时接受抗TNF-α抗体的动物器官中的菌落计数显著更高。将抗TNF-α抗体与两性霉素B或氟康唑联合使用并不影响真菌的形态或肾脏中的炎症反应。这项研究表明，外源性TNF-α以及可增加宿主内源性TNF-α产生的药物可能是氟康唑和两性霉素B治疗系统性念珠菌病的有用辅助药物。
