Enhancement of simian varicella virus infection in African green monkeys by recombinant human tumor necrosis factor alpha.
Enhancement of simian varicella virus infection in African green monkeys by recombinant human tumor necrosis factor alpha.
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重组人肿瘤坏死因子α增强非洲绿猴体内的猿水痘病毒感染。
DOI：
10.1093/infdis/159.2.331
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Liggitt,D
中科院分区：
文献类型：
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作者：
Soike,KF;Czarniecki,CW;Baskin,G;Blanchard,J;Liggitt,D
材料和方法猴SVV感染和应用抗病毒药物的抗病毒活性评价已有报道[8，9]。总之，用1.5×105pfu的SVV气管内联合皮下注射感染12只无SVV抗体的猴。重组人肿瘤坏死因子-α是在大肠杆菌[2]中生产的，并在基因技术公司(加利福尼亚州旧金山南部)进行了纯化和鉴定。在2毫升溶液中含有1毫克重组人肿瘤坏死因子-a的小瓶含有*c：0.025 pg/毫克蛋白质，根据凝胶变形细胞裂解试验(LAL)测定[10]。每天在含人血清白蛋白(2 mg/mL)的PBS(pH 7.2)中制备稀释液。将重组人肿瘤坏死因子-α按10、3或1 ng/kg的剂量每日分两次静脉注射给猴，每组3只。三只受感染的对照猴子接受了不含rHuTNF-a的PBS安慰剂注射，注射程序相同。用rHuTNF-a治疗SVV感染的猴子在接种病毒后24小时开始，这一时间段已经显示出对a和(3)干扰素的治疗效果[8，9]，我们选择了rHuTNF-a的给药剂量和给药途径，这些剂量和给药途径在以前对未感染的猴子的研究和对癌症患者的I期研究中被证明是有效的[11，12]。
Materials and MethodsSVV infection of monkeys and evaluation of antiviral ac-tivity of administered antiviral drugs has previously been described [8, 9]. In brief, 12 monkeys free of antibody to SVV were infected by combined intratracheal and sc in-oculation of 1.5 x 105 pfu of SVV. rHuTNF-a was pro-duced in Escherichia coli [2] and was purified and characterized at Genentech (South San Francisco, Calif). Vials containing 1 mg of rHuTNF-a in 2 mL of solution contained* c: 0.025 pg of endotoxin/mg of protein, as determined by the Limulus amoebocyte lysate (LAL) assay [10]. Dilutions were prepared daily in PBS (pH 7.2) containing human serum albumin (2 mg/mL). The rHuTNF-a, at doses of 10, 3, or 1 ng/kg per day, was administered in divided doses twice daily to groups of three monkeys by iv bolus injection into the saphenous vein. Three infected control monkeys received a placebo injection of PBS without rHuTNF-a, administered on the same injection schedule. Treatment of SVV-infected monkeys with rHuTNF-a began 24 h after inoculation of virus, a timeframe that has shown therapeutic efficacy with the a and (3 interferons [8, 9], We selected doses and routes of administra-tion of rHuTNF-a that have been shown to be well toler-ated and efficacious in previous studies of uninfected monkeys and in phase I studies in patients with cancer [11, 12].