Doki Tomoyoshi, Takano Tomomi, Kawagoe Kohei, Kito Akihiko, Hohdatsu Tsutomu
Laboratory of Veterinary Infectious Disease, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan.
Res Vet Sci. 2016 Feb;104:17-23. doi: 10.1016/j.rvsc.2015.11.005. Epub 2015 Nov 12.
Feline infectious peritonitis virus (FIPV) replication in macrophages/monocytes induced tumor necrosis factor (TNF)-alpha production, and that the TNF-alpha produced was involved in aggravating the pathology of FIP. We previously reported the preparation of a feline TNF-alpha (fTNF-alpha)-neutralizing mouse monoclonal antibody (anti-fTNF-alpha mAb). This anti-fTNF-alpha mAb 2-4 was confirmed to inhibit the following fTNF-alpha-induced conditions in vitro. In the present study, we investigated whether mAb 2-4 improved the FIP symptoms and survival rate of experimentally FIPV-inoculated SPF cats. Progression to FIP was prevented in 2 out of 3 cats treated with mAb 2-4, whereas all 3 cats developed FIP in the placebo control group. Plasma alpha1-glycoprotein and vascular endothelial growth factor levels were improved by the administration of mAb 2-4, and the peripheral lymphocyte count also recovered. These results strongly suggested that the anti-fTNF-alpha antibody is effective for the treatment of FIP.
猫传染性腹膜炎病毒(FIPV)在巨噬细胞/单核细胞中的复制诱导肿瘤坏死因子(TNF)-α的产生,且所产生的TNF-α参与加重FIP的病理过程。我们之前报道了猫TNF-α(fTNF-α)中和小鼠单克隆抗体(抗fTNF-α mAb)的制备。已证实这种抗fTNF-α mAb 2-4在体外可抑制以下fTNF-α诱导的情况。在本研究中,我们调查了mAb 2-4是否改善了经实验性接种FIPV的SPF猫的FIP症状和存活率。用mAb 2-4治疗的3只猫中有2只预防了FIP的进展,而安慰剂对照组的3只猫均发生了FIP。给予mAb 2-4可改善血浆α1-糖蛋白和血管内皮生长因子水平,外周淋巴细胞计数也恢复正常。这些结果强烈表明抗fTNF-α抗体对FIP治疗有效。