摘要目的 探讨新型细胞因子自细胞介素(IL)-33在胶原诱导性关节炎(CIA)发病中的作用.方法 建它DBA/1小鼠的CIA模型.以牛Ⅱ型胶原(CⅡ)/完全福氏佐剂(CFA)免疫,从免疫后第21天开始每天注射IL-33或磷酸盐缓冲液(PBS)共5 d.免疫后第28天取小鼠淋巴结细胞体外培养,培养上清的细胞因子浓度以酶联免疫吸附试验(ELISA)法检测或Luminex检测.同时检测血清中抗Ⅱ型胶原抗体和血清中的细胞因子浓度.鼠爪脱钙后行病理检查.采用两样本均数的t检验、χ~2检验进行统计学处理.结果 IL-33可使小鼠实验性的关节炎发病加重,致炎性细胞因子和抗Ⅱ型胶原抗体产生增多(P<0.05).PBS组与IL-33组的IgG2a型Ⅱ型胶原抗体为[(1.24±0.33)mg/L和(1.96±0.16)mg/L,P<0.05],而IgG1型抗Ⅱ型胶原抗体为[(1.1±0.4)ms/L和(1.7±0.4)mg/L,P<0.05).结论 IL-33是炎性关节病中的重要致炎因子.这一IL-1家族新成员是潜在的类风湿关节炎(RA)治疗靶点.

abstractsObjective To explore the role of a new cytokine interleukin (IL)-33 in collagen induced arthritis (CIA). Methods The murine model of CIA was employed. DBA/1 mice were immunized with C Ⅱ/CFA and challenged with the same dose of C Ⅱ in PBS on day 21. The mice were injected I.p daily with IL-33 or PBS for 5 clays from day 21. Lymphonodes were removed on day 28 after primary immunization and cultured. The concentrations of all eytokines of the supernatants were determined by ELISA or an 20-plex-mouse cyto-kine assay according to the manufacturer's instructions. Serum anti-C Ⅱ antibody and mice paw histology were. Also assessed. Two independent samples t test, chi-square test were used for statistical analysis. Results DBA/1 mice receiving IL-33 injection exhibited an exacerbated CIA both in terms of clinical evaluation and histological parameters. IL-17, IFN-γ, TNF-α, IL-5, IL-12, GM-CSF, MCP-1 and IP-10 productions were also elevated in IL-33 group (P<0.05). Similarly, mice in the IL-33 injection group had higher levels of anti-collagen antibodies compared with those of the controls. The concentrations of C Ⅱ-specific IgG2a were [(1.96±0.16) vs (1.24±sO.33) mg/L] (P<0.05), while IgG1 anti-C Ⅱ antibodies were [ (1.1±0.4) vs (1.7±0.4) mg/L] (P<0.05). Conclusion IL-33 is a critical pro-inflammatory cytokine for inflamm-atory joint disease. Thus this novel IL-1 supeffamily member represents a novel therapeutic target for rheumatoid arthritis ( RA ).