Weiner H L
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Annu Rev Med. 1997;48:341-51. doi: 10.1146/annurev.med.48.1.341.
Orally administered autoantigens suppress autoimmunity in animal models, including experimental allergic encephalomyelitis, collagen and adjuvant-induced arthritis, uveitis, and diabetes in the non-obese diabetic mouse. Low doses of oral antigen induce antigen-specific regulatory T-cells in the gut, which act by releasing inhibitory cytokines such as transforming growth factor-beta, interleukin-4, and interleukin-10 at the target organ. Thus, one can suppress inflammation at a target organ by orally administering an antigen derived from the site of inflammation, even if it is not the target of the autoimmune response. Initial human trials of orally administered antigen have shown positive findings in patients with multiple sclerosis and rheumatoid arthritis. A double-blind, placebo-controlled, phase III multi-center trial of oral myelin in 515 relapsing-remitting multiple sclerosis patients is in progress, as are phase II clinical trials investigating the oral administration of type II collagen in rheumatoid arthritis, S-antigen in uveitis, and insulin in type I diabetes.
口服自身抗原可在动物模型中抑制自身免疫，包括实验性变态反应性脑脊髓炎、胶原和佐剂诱导的关节炎、葡萄膜炎，以及非肥胖糖尿病小鼠的糖尿病。低剂量口服抗原可在肠道诱导抗原特异性调节性T细胞，这些细胞通过在靶器官释放抑制性细胞因子（如转化生长因子-β、白细胞介素-4和白细胞介素-10）发挥作用。因此，即使抗原不是自身免疫反应的靶标，通过口服源自炎症部位的抗原也可以抑制靶器官的炎症。口服抗原的初步人体试验已在多发性硬化症和类风湿性关节炎患者中显示出阳性结果。一项针对515例复发缓解型多发性硬化症患者的口服髓磷脂双盲、安慰剂对照III期多中心试验正在进行中，同时也在进行II期临床试验，研究类风湿性关节炎中口服II型胶原、葡萄膜炎中口服S抗原以及I型糖尿病中口服胰岛素的效果。
