Kuga Kazufumi, Nishifuji Koji, Iwasaki Toshiroh
Department of Veterinary Medicine, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan.
J Vet Med Sci. 2008 Oct;70(10):1011-6. doi: 10.1292/jvms.70.1011.
Cyclosporine A (CsA) has been widely used for suppression of transplant rejection and controlling pruritus in allergic dermatitis in humans, dogs and cats. CsA is known to suppress the expression of inflammatory cytokines, including IL-2, IL-4, IFN-gamma and TNF-alpha in humans, dogs and experimental mice. However, little is known about the immunomodulating effect of CsA in cats. The aim of this study was to evaluate the effects of CsA on the expression of inflammatory cytokines in feline peripheral blood mononuclear cells (PBMC). Real-time PCR analyses with Concanavalin A (ConA)-stimulated PBMC obtained from 5 cats revealed that the expression of mRNAs for IL-2, IL-4, IFN- gamma and TNF-alpha was inhibited by CsA in a dose-dependent manner. Moreover, an enzyme-linked immunospot (ELISPOT) assay, which is capable of detecting IL-2 secreting cells as single spots, revealed that the frequency of IL-2 secreting cells in ConA-stimulated feline PBMC was significantly reduced in the presence of CsA. These results might provide an explanation for the mechanisms of action of CsA in the suppression of transplant rejection and the control of pruritus in cats.
环孢素A(CsA)已被广泛用于抑制人类、犬类和猫类的移植排斥反应以及控制过敏性皮炎中的瘙痒。已知CsA可抑制人类、犬类和实验小鼠中包括白细胞介素-2(IL-2)、白细胞介素-4(IL-4)、干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)在内的炎性细胞因子的表达。然而,CsA在猫体内的免疫调节作用却鲜为人知。本研究的目的是评估CsA对猫外周血单个核细胞(PBMC)中炎性细胞因子表达的影响。对从5只猫获取的经刀豆蛋白A(ConA)刺激的PBMC进行实时PCR分析显示,CsA以剂量依赖的方式抑制IL-2、IL-4、IFN-γ和TNF-α的mRNA表达。此外,一种能够将分泌IL-2的细胞检测为单个斑点的酶联免疫斑点(ELISPOT)分析表明,在有CsA存在的情况下,ConA刺激的猫PBMC中分泌IL-2的细胞频率显著降低。这些结果可能为CsA在猫体内抑制移植排斥反应和控制瘙痒的作用机制提供解释。