Morikage T, Mizushima Y, Sakamoto K, Yano S
First Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan.
Cancer Res. 1990 Apr 1;50(7):2099-104.
The preventive capability of interleukin 1 alpha (IL-1) against bacterial infections was estimated in normal and anticancer drug-treated BALB/c mice in comparison with OK432, granulocyte colony-stimulating factor, interferons alpha and gamma, and interleukin 2. Pretreatment with IL-1 (days -4 and -2) resulted in a significantly higher survival rate in normal mice inoculated i.p. with Klebsiella pneumoniae, Pseudomonas aeruginosa or Listeria monocytogenes (day 0). The i.p. and s.c. administrations of IL-1 were equally effective for the induction of antibacterial resistance. Pretreatment with OK432 showed an equal degree of resistance to i.p. infection but was effective only by i.p. administration. Enhanced antibacterial resistance by IL-1 and OK432 was also observed in cyclophosphamide- and aminomethylpyrimidinylmethylchloroethylnitrosourea hydrochloride-pretreated (day -5) normal hosts and in cyclophosphamide-treated tumor-bearing hosts. In the case of granulocyte colony-stimulating factor (i.p. or s.c.) (days -4 to -1), a statistical difference in survival rate between granulocyte colony-stimulating factor and its vehicle-treated groups was observed in cyclophosphamide-pretreated hosts, but not in normal hosts or aminomethylpyrimidinylmethylchloroethylnitrosourea hydrochloride-pretreated hosts. Viable bacteria in the peritoneal cavity and blood at 12 h after i.p. infection of K. pneumoniae correlated well with the survival rate. In IL-1-pretreated hosts, the earlier and increased accumulation of neutrophils into peritoneal cavity after the infection was observed and the number of inflammatory cells in peritoneal cavity correlated well with the survival rate. The enhanced resistance to bacterial infection by IL-1 was suggested to be in part due to the enhanced cellular defense mechanisms. The prophylactic administration of IL-1 would be beneficial for the management of serious infections in cancer patients.
与溶链菌制剂OK432、粒细胞集落刺激因子、α和γ干扰素以及白细胞介素2相比，评估了白细胞介素1α（IL-1）对正常小鼠和接受抗癌药物治疗的BALB/c小鼠细菌感染的预防能力。用IL-1预处理（第-4天和-2天），导致经腹腔接种肺炎克雷伯菌、铜绿假单胞菌或单核细胞增生李斯特菌（第0天）的正常小鼠存活率显著更高。IL-1的腹腔内和皮下给药在诱导抗菌抗性方面同样有效。用OK432预处理显示出对腹腔感染同等程度的抗性，但仅通过腹腔给药有效。在环磷酰胺和盐酸氨甲嘧啶基甲基氯乙基亚硝基脲预处理（第-5天）的正常宿主以及环磷酰胺治疗的荷瘤宿主中，也观察到IL-1和OK432增强的抗菌抗性。对于粒细胞集落刺激因子（腹腔内或皮下）（第-4天至-1天），在环磷酰胺预处理的宿主中观察到粒细胞集落刺激因子与其载体处理组之间存活率的统计学差异，但在正常宿主或盐酸氨甲嘧啶基甲基氯乙基亚硝基脲预处理的宿主中未观察到。腹腔感染肺炎克雷伯菌后12小时腹腔和血液中的活菌数与存活率密切相关。在IL-1预处理的宿主中，观察到感染后中性粒细胞更早且更多地积聚到腹腔中，腹腔中的炎症细胞数量与存活率密切相关。提示IL-1增强的对细菌感染的抗性部分归因于增强的细胞防御机制。IL-1的预防性给药对癌症患者严重感染的管理将是有益的。
