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抗人 TNF-α 抗体和伊曲康唑治疗猫传染性腹膜炎的疗效。

Therapeutic effect of an anti-human-TNF-alpha antibody and itraconazole on feline infectious peritonitis.

机构信息

Laboratory of Veterinary Infectious Disease, School of Veterinary Medicine, Kitasato University, Towada, Aomori, 034-8628, Japan.

出版信息

Arch Virol. 2020 May;165(5):1197-1206. doi: 10.1007/s00705-020-04605-7. Epub 2020 Mar 31.

Abstract

Feline infectious peritonitis (FIP) is a fatal disease in wild and domestic cat species. Although several drugs are expected to be useful as treatments for FIP, no drugs are available in clinical practice. In this study, we evaluated the therapeutic effect of combined use of adalimumab (an anti-human-TNF-alpha monoclonal antibody, ADA) and itraconazole (ICZ), which are presently available to veterinarians. The neutralizing activity of ADA against fTNF-alpha-induced cytotoxicity was measured in WEHI-164 cells. Ten specific pathogen-free (SPF) cats were inoculated intraperitoneally with type I FIPV KU-2. To the cats that developed FIP, ADA (10 mg/animal) was administered twice between day 0 and day 4 after the start of treatment. ICZ (50 mg/head, SID) was orally administered daily from day 0 after the start of treatment. ADA demonstrated dose-dependent neutralizing activity against rfTNF-alpha. In an animal experiment, 2 of 3 cats showed improvements in FIP clinical symptoms and blood chemistry test results, an increase in the peripheral blood lymphocyte count, and a decrease in the plasma alpha 1-AGP level were observed after the beginning of treatment. One of the cats failed to respond to treatment and was euthanized, although the viral gene level in ascites temporarily decreased after the start of treatment. ADA was found to have neutralizing activity against rfTNF-alpha. The combined use of ADA and ICZ showed a therapeutic effect for experimentally induced FIP. We consider these drugs to be a treatment option until effective anti-FIPV drugs become available.

摘要

猫传染性腹膜炎(Feline infectious peritonitis,FIP)是一种致命性疾病,可感染野生和家猫。尽管有几种药物被认为对 FIP 治疗可能有效,但目前在临床实践中尚无可用的药物。在本研究中,我们评估了阿达木单抗(一种抗人 TNF-α单克隆抗体,ADA)和伊曲康唑(itraconazole,ICZ)联合使用的治疗效果,这两种药物目前均可供兽医使用。在 WEHI-164 细胞中测量了 ADA 对 fTNF-α诱导的细胞毒性的中和活性。将 10 只特定病原体无(specific pathogen free,SPF)猫经腹腔接种 I 型 FIPV KU-2。对发生 FIP 的猫,在治疗开始后第 0 天至第 4 天之间,每只猫给予 ADA(10 mg/动物)两次。从治疗开始后的第 0 天起,每天口服 ICZ(50 mg/头,SID)。ADA 对 rfTNF-α表现出剂量依赖性的中和活性。在动物实验中,3 只猫中有 2 只猫的 FIP 临床症状和血液化学检测结果得到改善,外周血淋巴细胞计数增加,血浆α1-AGP 水平降低,在开始治疗后观察到。其中一只猫对治疗没有反应,被安乐死,尽管在开始治疗后腹水内的病毒基因水平暂时下降。ADA 被发现对 rfTNF-α具有中和活性。ADA 和 ICZ 的联合使用对实验诱导的 FIP 显示出治疗效果。我们认为,在有效抗 FIPV 药物问世之前,这些药物是一种治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b7e/7110289/f6b9761cb03c/705_2020_4605_Fig1_HTML.jpg

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