Zhang Rui, Qian Jiang, Guo Jie, Yuan Yi-Fei, Xue Kang
Department of Ophthalmology, Eye and ENT Hospital Affiliated to Fudan University, No. 83, Fenyang Road, Shanghai 200031, China.
Curr Eye Res. 2009 Apr;34(4):297-303. doi: 10.1080/02713680902741696.
To determine whether treatment with anti-IL-17 antibody could suppress the intraocular inflammation of experimental autoimmune uveoretinitis (EAU) in rats.
Rats were immunized with interphotoreceptor retinoid binding protein (IRBP) R16 peptide and were treated with anti-IL-17 antibody. Clinical signs of inflammation and ocular histological sections were observed and graded. Cytokine levels of supernatants of cells from draining lymph nodes were measured by enzyme-linked immunosorbent assay (ELISA). Delayed-type hypersensitivity (DTH) and lymphocyte proliferation assay (LPA) were detected.
Treatment of EAU with anti-IL-17 antibody delayed the onset of ocular inflammation and markedly inhibited the development of EAU. Antigen-specific DTH and LPA were suppressed, whereas the level of interferon (IFN)-gamma produced by draining lymph node cells was increased after treatment with anti-IL-17 antibody. There was no significant change of IL-5 level as compared with control rats.
These findings demonstrate that blockade of endogenous IL-17 activity by treatment with anti-IL-17 antibody attenuates EAU in rats. IL-17 rather than IFN-gamma plays a crucial role in the development of EAU, and that antagonism of IL-17 could be useful for the treatment of human intraocular autoimmune diseases.
确定抗白细胞介素-17(IL-17)抗体治疗是否能抑制大鼠实验性自身免疫性葡萄膜视网膜炎(EAU)的眼内炎症。
用视网膜色素上皮间维生素A结合蛋白(IRBP)R16肽免疫大鼠,并给予抗IL-17抗体治疗。观察并分级炎症的临床体征和眼部组织学切片。通过酶联免疫吸附测定(ELISA)测量引流淋巴结细胞上清液中的细胞因子水平。检测迟发型超敏反应(DTH)和淋巴细胞增殖试验(LPA)。
用抗IL-17抗体治疗EAU可延迟眼内炎症的发作,并显著抑制EAU的发展。抗原特异性DTH和LPA受到抑制,而用抗IL-17抗体治疗后,引流淋巴结细胞产生的干扰素(IFN)-γ水平升高。与对照大鼠相比,IL-5水平无显著变化。
这些发现表明,用抗IL-17抗体治疗阻断内源性IL-17活性可减轻大鼠的EAU。IL-17而非IFN-γ在EAU的发展中起关键作用,并且拮抗IL-17可能对治疗人类眼内自身免疫性疾病有用。