Wendling U, Bloemendal A, Van Der Zee R, Rutten V P, Van Kooten P J, Farine J C, Van Eden W
Institute for Infectious Diseases and Immunology, Utrecht University, The Netherlands.
Int J Immunopharmacol. 1997 Sep-Oct;19(9-10):565-8. doi: 10.1016/s0192-0561(97)00084-2.
Oral administration of E. coli extract OM-89 is used in treating RA. It has been shown that immune reactivity to heat-shock proteins (hsp) is involved in immunomodulation of arthritis. We evaluated the postulated presence and immunogenicity of hsp's in OM-89. The effects of OM-89 in experimental arthritis were analyzed. Proliferative T cell responses to bacterial hsp60 and hsp70 were found in rats immunized with OM-89. And conversely, immunization with hsp antigens induced OM-89-specific T cell responses. Hsp70 (DnaK) was found to be a major immunogenic constituent of OM-89. Parenteral immunization with OM-89 reduces resistance to adjuvant arthritis (AA), whereas oral administration protects against AA. Given the arthritis inhibitory effect of oral OM-89 in AA our findings suggest peripheral tolerance induced by hsp-specific regulatory T cells as a mode of action for OM-89 as an arthritis suppressive oral drug.
口服大肠杆菌提取物OM-89可用于治疗类风湿性关节炎(RA)。研究表明,对热休克蛋白(hsp)的免疫反应性参与了关节炎的免疫调节。我们评估了OM-89中hsp的假定存在情况及其免疫原性。分析了OM-89在实验性关节炎中的作用。在用OM-89免疫的大鼠中发现了对细菌hsp60和hsp70的增殖性T细胞反应。相反,用hsp抗原免疫可诱导OM-89特异性T细胞反应。发现hsp70(DnaK)是OM-89的主要免疫原性成分。经肠胃外免疫OM-89会降低对佐剂性关节炎(AA)的抵抗力,而口服则可预防AA。鉴于口服OM-89对AA具有关节炎抑制作用,我们的研究结果表明,hsp特异性调节性T细胞诱导的外周耐受是OM-89作为一种抑制关节炎的口服药物的作用方式。