Louie A, Baltch A L, Franke M A, Ritz W J, Smith R P, Singh J K, Gordon M A
Infectious Disease Section, Stratton Veterans Affairs Medical Center, Albany, New York 12208, USA.
J Antimicrob Chemother. 1996 May;37(5):943-54. doi: 10.1093/jac/37.5.943.
Pentoxifylline can decrease the production of tumour necrosis factor alpha (TNF alpha) by endotoxin-stimulated macrophages and may improve survival in animals with overwhelming bacterial sepsis. In this study various doses of pentoxifylline were administered to mice with systemic Candida albicans infection to determine its effect on serum TNF alpha levels, organ fungal burden, and host survival. Intraperitoneal injections of pentoxifylline at 20 mg/kg every 8 h did not affect these endpoints. However, fungal counts were significantly higher in kidneys of animals that received 30 and 60 mg/kg of pentoxifylline every 8 h when compared to controls. Injection of 60 mg/kg of pentoxifylline at 8 h intervals also significantly shortened mean survival from 5.8 to 3.8 days (P = 0.01). Pentoxifylline did not affect peripheral WBC counts, serum TNF alpha and interleukin-6 levels, or the density of neutrophils in tissues. In vitro, pentoxifylline decreased the production of TNF alpha by C. albicans-stimulated macrophages in a dose-dependent manner, but only at concentrations greater than 100 mg/L. In contrast, pentoxifylline suppressed TNF alpha production by endotoxin-stimulated macrophages at concentrations as low as 10 mg/L. Thus, higher doses of pentoxifylline are detrimental in systemic C. albicans infection. However, the detrimental effect is not mediated by alterations in serum TNF alpha or interleukin-6 levels or the aggregation of neutrophils in tissues.
己酮可可碱可减少内毒素刺激的巨噬细胞产生肿瘤坏死因子α（TNFα），并可能提高患有严重细菌性败血症动物的存活率。在本研究中，对患有系统性白色念珠菌感染的小鼠给予不同剂量的己酮可可碱，以确定其对血清TNFα水平、器官真菌负荷和宿主存活率的影响。每8小时腹腔注射20mg/kg己酮可可碱对这些指标没有影响。然而，与对照组相比，每8小时接受30mg/kg和60mg/kg己酮可可碱的动物肾脏中的真菌计数显著更高。每隔8小时注射60mg/kg己酮可可碱也显著缩短了平均存活时间，从5.8天缩短至3.8天（P = 0.01）。己酮可可碱不影响外周白细胞计数、血清TNFα和白细胞介素-6水平，或组织中中性粒细胞的密度。在体外，己酮可可碱以剂量依赖的方式降低白色念珠菌刺激的巨噬细胞产生TNFα，但仅在浓度大于100mg/L时。相比之下，己酮可可碱在低至10mg/L的浓度下就能抑制内毒素刺激的巨噬细胞产生TNFα。因此，高剂量的己酮可可碱在系统性白色念珠菌感染中是有害的。然而，这种有害作用不是由血清TNFα或白细胞介素-6水平的改变或组织中中性粒细胞的聚集介导的。
