Sartani G, Silver P B, Strassmann G, Chan C C, Caspi R R
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892, USA.
Curr Eye Res. 1995 Oct;14(10):887-96. doi: 10.3109/02713689508995128.
The experimental drug suramin has been shown to possess several immunosuppressive properties. In this study we investigated the effect of suramin on the development of experimental autoimmune uveoretinitis (EAU) in mice and in rats. EAU was induced either by active immunization with a uveitogenic protein or peptide, or by the adoptive transfer of a uveitogenic T cell line. The development of EAU was assessed by clinical evaluation as well as by histopathology. Immunological responses were measured by delayed type hypersensitivity (DTH), lymphocyte proliferation, and serum antibody levels to the immunizing antigen. Suramin treatment was most effective in suppressing EAU when started concurrently with immunization (afferent). Treatment was less effective in suppressing disease when first administered 7 days after immunization or when given to animals that received an adoptive transfer of uveitogenic T cells (efferent). The effect of suramin on DTH and lymphocyte proliferation roughly paralleled its effect on EAU. Aferent treatment of mice with suramin completely suppressed anti-IRBP antibody titers. Interestingly, animals receiving efferent treatment had unreduced IgM levels but little or no IgG, suggesting prevention of the IgM-to-IgG switch. Depressed in vitro lymphocyte proliferative responses in animals treated with suramin during the afferent stage suggested that the suppressive effect on disease was due at least in part to an inhibition of antigen priming. Our results suggest that suramin merits further investigation as a potential treatment for some types of uveitis.
实验性药物苏拉明已被证明具有多种免疫抑制特性。在本研究中，我们调查了苏拉明对小鼠和大鼠实验性自身免疫性葡萄膜视网膜炎（EAU）发展的影响。EAU通过用致葡萄膜炎蛋白或肽进行主动免疫诱导，或通过致葡萄膜炎T细胞系的过继转移诱导。通过临床评估以及组织病理学评估EAU的发展。通过迟发型超敏反应（DTH）、淋巴细胞增殖以及针对免疫抗原的血清抗体水平来测量免疫反应。当与免疫（传入）同时开始时，苏拉明治疗在抑制EAU方面最有效。在免疫后7天首次给药时，或给予接受致葡萄膜炎T细胞过继转移的动物（传出）时，治疗在抑制疾病方面效果较差。苏拉明对DTH和淋巴细胞增殖的影响大致与其对EAU的影响平行。用苏拉明对小鼠进行传入治疗可完全抑制抗IRBP抗体滴度。有趣的是，接受传出治疗的动物IgM水平未降低，但IgG很少或没有，这表明预防了IgM向IgG的转换。在传入阶段用苏拉明治疗的动物中，体外淋巴细胞增殖反应受到抑制，这表明对疾病的抑制作用至少部分归因于对抗原启动的抑制。我们的结果表明，苏拉明作为某些类型葡萄膜炎的潜在治疗方法值得进一步研究。
