Niedbala W, Cai B, Wei X, Patakas A, Leung B P, McInnes I B, Liew F Y
Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, UK.
Ann Rheum Dis. 2008 Oct;67(10):1474-9. doi: 10.1136/ard.2007.083360. Epub 2008 Jan 16.
To investigate the potential role of interleukin (IL) 27 in rheumatoid arthritis (RA) by examining the expression of IL27 in the articular joints of patients with RA and the effect of recombinant IL27 in vivo in a murine model of collagen-induced arthritis (CIA).
Synovial membranes from patients with RA were examined for the presence of IL27 by immunohistochemistry and by western blot. Mice developing CIA were treated with IL27 and the ensuing disease progression and immunological profile determined. The effect of IL27 on T-cell response in vitro was also ascertained.
IL27 was clearly detected in the RA synovial membranes. Short-term administration of IL27 at the onset of the disease significantly attenuated disease severity compared with untreated controls. Histological examination showed that while untreated mice developed severe cellular infiltration in the joints, synovial hyperplasia and joint erosion, this pathology was profoundly reduced in IL27-treated animals. Treatment of mice with IL27 also decreased the amounts of serum IL6 and collagen-specific IgG2a. Spleen and lymph node cells from the IL27-treated mice produced significantly less interferon gamma and IL17 than cells from the control mice when cultured with collagen in vitro.
These results demonstrate that IL27 may be a potential therapeutic agent against RA at the onset of the disease.
通过检测类风湿关节炎(RA)患者关节中白细胞介素(IL)27的表达以及重组IL27在胶原诱导性关节炎(CIA)小鼠模型中的体内作用,研究IL27在RA中的潜在作用。
采用免疫组织化学和蛋白质印迹法检测RA患者滑膜组织中IL27的存在情况。用IL27治疗患CIA的小鼠,并确定随后的疾病进展和免疫特征。还确定了IL27对体外T细胞反应的影响。
在RA滑膜组织中可清楚检测到IL27。与未治疗的对照组相比,在疾病发作时短期给予IL27可显著减轻疾病严重程度。组织学检查显示,未治疗的小鼠关节出现严重的细胞浸润、滑膜增生和关节侵蚀,而在接受IL27治疗的动物中,这种病理变化明显减轻。用IL27治疗小鼠还可降低血清IL6和胶原特异性IgG2a的水平。当与胶原在体外共同培养时,来自接受IL27治疗小鼠的脾细胞和淋巴结细胞产生的干扰素γ和IL17明显少于对照组小鼠的细胞。
这些结果表明,IL27可能是疾病发作时抗RA的一种潜在治疗药物。