Chang D M
Rheumatology/Immunology/Allergy, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, R.O.C.
Immunopharmacol Immunotoxicol. 1995 Aug;17(3):437-50. doi: 10.3109/08923979509016380.
Investigative attempts to identify novel therapy for inflammatory connective tissue diseases continue to evolve. Amiprilose hydrochloride (amiprilose HCl) is a synthetic carbohydrate shown to have anti-inflammatory effects in animal models of inflammatory arthritis and in a multicenter clinical trial. Interleukin-1 (IL-1) is an important mediator of immune regulation, inflammation and joint destruction in arthritis. In the present study, the effects of amiprilose HCl on IL-1 activity, production and receptor distribution were investigated. Drug effects on IL-2 production and receptor distribution on lymphocytes were also explored. Potential regulation of IL-1 activity was determined by monitoring the effects of amiprilose HCl on IL-1 stimulated proliferation of murine thymocytes and human synovial cells. Inhibitory effects on IL-1 beta and IL-2 production by stimulated human peripheral blood monocytes were measured by ELISA and lymphocyte IL-1 beta and IL-2 receptor distribution were analyzed by flow cytometry. The results from in vitro studies demonstrated that low concentrations of amiprilose HCl (1-100 micrograms/ml) stimulated thymocyte proliferation and enhanced the proliferative response of IL-1 stimulated human synovial fibroblasts. IL-1 beta production in cultures of human peripheral blood monocytes was significantly decreased after exposure of the cultures to varying doses of amiprilose HCl as determined by ELISA. Exposure of mitogen activated human peripheral blood lymphocytes to amiprilose HCl resulted in decreased IL-2 production at high concentrations of drug as compared to control. However, at doses of amiprilose HCl previously found to stimulate thymocyte proliferation (1-10 micrograms/ml), increased levels of culture supernatant IL-2 were observed. No amiprilose HCl mediated changes in lymphocyte IL-1 beta or IL-2 receptor expression were observed. The regulatory effects of amiprilose HCl on cytokines support the potential of this drug as a therapeutic agent for the treatment of inflammatory arthritis.
确定炎症性结缔组织疾病新疗法的研究仍在不断发展。盐酸氨普立糖（amiprilose HCl）是一种合成碳水化合物，在炎症性关节炎动物模型和一项多中心临床试验中显示具有抗炎作用。白细胞介素-1（IL-1）是关节炎中免疫调节、炎症和关节破坏的重要介质。在本研究中，研究了盐酸氨普立糖对IL-1活性、产生及受体分布的影响。还探讨了该药物对淋巴细胞IL-2产生及受体分布的影响。通过监测盐酸氨普立糖对IL-1刺激的小鼠胸腺细胞和人滑膜细胞增殖的影响来确定对IL-1活性的潜在调节作用。通过酶联免疫吸附测定（ELISA）检测对人外周血单核细胞刺激产生的IL-1β和IL-2的抑制作用，并通过流式细胞术分析淋巴细胞IL-1β和IL-2受体分布。体外研究结果表明，低浓度的盐酸氨普立糖（1 - 100微克/毫升）刺激胸腺细胞增殖，并增强IL-1刺激的人滑膜成纤维细胞的增殖反应。根据ELISA测定，将人外周血单核细胞培养物暴露于不同剂量的盐酸氨普立糖后，培养物中IL-1β的产生显著降低。与对照相比，有丝分裂原激活的人外周血淋巴细胞暴露于盐酸氨普立糖后，在高浓度药物时IL-2产生减少。然而，在先前发现能刺激胸腺细胞增殖的盐酸氨普立糖剂量（1 - 10微克/毫升）下，观察到培养上清液中IL-2水平升高。未观察到盐酸氨普立糖介导的淋巴细胞IL-1β或IL-2受体表达变化。盐酸氨普立糖对细胞因子的调节作用支持了该药物作为治疗炎症性关节炎治疗剂的潜力。
