羧胺三唑对白细胞介素-1β介导自身炎症性疾病的治疗作用  

Therapeutic Effect of Carboxyamidotriazole on IL-1β-Mediated Autoinflammatory Diseases

作　　者：段梦园 沈敏 和仪 叶菜英[1] 朱蕾[1] DUAN Mengyuan;SHEN Min;HE Yi;YE Caiying;ZHU Lei(Department of Pharmacology,Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences and School of Basic Medicine,Peking Union Medical College,Bejing 100005,China;Deparement of Rheumatology and Clinical Immunology,Chinese Academy of Medical Science&Peking Union Medical College,National Clinical Research Center for Dermatology and Immunologic Disseases(NCRC-DID),Ministry of Science&Technology,State Key Laboratory of Complex Severe and Rare Disease,Peking Union Medical College Hospital(PUMOH),Key Laboratory of Rheumatology and Clinical Immunology,Ministry of Education,Beijing 100730,China)

机构地区：[1]中国医学科学院基础医学研究所,北京协和医学院基础学院药理系,北京100005 [2]中国医学科学院北京协和医学院北京协和医院风湿免疫科,国家皮肤与免疫疾病临床医学研究中心(NCRC-DID),疑难重症及罕见病国家重点实验室,风湿免疫病学教育部重点实验室,北京100730

出　　处：《医药导报》2023年第10期1502-1507,共6页Herald of Medicine

基　　金：中国医学科学院医学与健康科技创新工程(2021-I2M-1-005);北京协和医院中央高水平医院临床科研专项(2022-PUMCH-C-025)。

摘　　要：目的初步探索羧胺三唑(CAI)对核苷酸结合寡聚化结构域样受体蛋白12(NLRP12)相关自身炎症性疾病(NLRP12-AID)、家族性地中海热(FMF)和肿瘤坏死因子受体相关周期性综合征(TRAPS)等3种白细胞介素(IL)-1β介导自身炎症性疾病(AIDs)的治疗作用。方法分离患者外周血单核细胞(PBMCs),加入CAI培养后取细胞培养上清,酶联免疫吸附测定(ELISA)测定上清液中IL-1β、IL-6和肿瘤坏死因子(TNF)-α的水平。结果CAI明显降低NLRP12-AID患者PBMCs分泌IL-1β的水平(P<0.05或P<0.01),对IL-6和TNF-α水平有降低趋势,但差异无统计学意义;CAI对FMF患者PBMCs分泌IL-1β、IL-6和TNF-α水平有不同程度降低作用(P<0.05或P<0.01);CAI降低TRAPS患者PBMCs分泌IL-1β水平(P<0.05),对IL-6水平有降低趋势,但差异无统计学意义。结论CAI可能通过减少IL-1β等促炎细胞因子产生从而具有治疗NLRP12-AID、FMF和TRAPS等3种IL-1β介导AIDs的作用。Objective To preliminarily explore the effects of carboxyamidotriazole(CAI)on three kinds of interleukin(IL)-1β-mediated autoinflammatory diseases(AIDs)including NLRP12-associated autoinflammatory disease(NLRP12-AID),familial Mediterranean fever(FMF),and tumor necrosis factor receptor-associated periodic syndrome(TRAPS).Methods Peripheral blood mononuclear cells(PBMCs)were isolated from AIDs patients and treated with CAI,and the levels of IL^(-1)β,IL-6 and tumour necrosis factor(TNF)-αin the culture supernatants were determined by enzyme linked immunosorbent assay(ELISA).Results CAI significantly reduced the level of IL^(-1)βsecretion from NLRP12-AID PBMCs(P<0.05 or P<0.01),and had a tendency to decrease IL-6 and TNF-αlevels,but the difference was not statistically significant(P>0.05).Also,CAI lowered the levels of IL^(-1)β,IL-6 and TNF-αsecreted by FMF PBMCs to different degree(P<0.05 or P<0.01);and lessened IL^(-1)βsecretion levels from TRAPS PBMCs.Conclusion CAI might have a role in treating three IL^(-1)β-mediated AIDs,including NLRP12-AID,FMF and TRAPS,by reducing the production of proinflammatory cytokines such as IL^(-1)β.

关 键 词：羧胺三唑 IL-1β介导自身炎症性疾病 NLRP12相关自身炎症性疾病 家族性地中海热 肿瘤坏死因子受体相关周期性综合征 细胞因子 

分 类 号：R979.5[医药卫生—药品] R593.2[医药卫生—药学]