Benito M J, Veale D J, FitzGerald O, van den Berg W B, Bresnihan B
Department of Rheumatology, Education and Research Centre, St Vincent's University Hospital, Dublin, Ireland.
Ann Rheum Dis. 2005 Sep;64(9):1263-7. doi: 10.1136/ard.2004.025270. Epub 2005 Feb 24.
To compare selected immunohistological features of inflammation in synovial tissue from patients with early and late osteoarthritis (OA).
Synovial tissue samples were obtained from 10 patients with knee pain, normal radiographs, and arthroscopic manifestations of OA (early OA), and from 15 patients with OA undergoing knee joint arthroplasty (late OA). Conventional immunohistochemical techniques were used to measure microscopic manifestations of inflammation. The inflammatory cell infiltrate, blood vessel formation, and angiogenic factors, NF-kappaB activation, expression of tumour necrosis factor alpha (TNFalpha) and interleukin 1beta (IL1beta), and the presence of cyclo-oxygenase (COX)-1 and COX-2 were quantified. Fibroblast-like synoviocytes (FLS) were isolated from early and late OA tissue samples to compare in vitro production of prostaglandin E2 (PGE2)
Synovial tissue from patients with early OA demonstrated significantly greater CD4+ (p = 0.017) and CD68+ (p<0.001) cell infiltration, blood vessel formation (p = 0.01), vascular endothelial growth factor (p = 0.001), and intercellular adhesion molecule-1 expression (p<0.001). Numbers of cells producing TNFalpha and IL1beta were also significantly greater in early OA (p<0.001). Manifestations of inflammation in early OA were associated with increased expression of the NF-kappaB1 (p<0.001) and RelA (p = 0.015) subunits, and with increased COX-2 expression (p = 0.04). Cytokine-induced PGE2 production by cultured FLS was similar in both groups.
Increased mononuclear cell infiltration and overexpression of mediators of inflammation were seen in early OA, compared with late OA. Isolated FLS were functionally similar in both groups, consistent with microenvironmental differences in the synovial tissue during different phases of OA. These observations may have important therapeutic implications for some patients during the early evolution of OA.
比较早期和晚期骨关节炎(OA)患者滑膜组织炎症的选定免疫组织学特征。
从10例有膝关节疼痛、X线片正常且有关节镜下OA表现的患者(早期OA)以及15例接受膝关节置换术的OA患者(晚期OA)获取滑膜组织样本。采用传统免疫组织化学技术测量炎症的微观表现。对炎性细胞浸润、血管形成、血管生成因子、NF-κB激活、肿瘤坏死因子α(TNFα)和白细胞介素1β(IL1β)的表达以及环氧化酶(COX)-1和COX-2的存在情况进行定量分析。从早期和晚期OA组织样本中分离出成纤维样滑膜细胞(FLS),以比较体外前列腺素E2(PGE2)的产生情况。
早期OA患者的滑膜组织显示CD4 +(p = 0.017)和CD68 +(p <0.001)细胞浸润、血管形成(p = 0.01)、血管内皮生长因子(p = 0.001)以及细胞间黏附分子-1表达(p <0.001)显著增加。早期OA中产生TNFα和IL1β的细胞数量也显著更多(p <0.001)。早期OA的炎症表现与NF-κB1(p <0.001)和RelA(p = 0.015)亚基的表达增加以及COX-2表达增加(p = 0.04)相关。两组中培养的FLS经细胞因子诱导产生的PGE2相似。
与晚期OA相比,早期OA中可见单核细胞浸润增加和炎症介质过度表达。两组中分离出的FLS在功能上相似,这与OA不同阶段滑膜组织的微环境差异一致。这些观察结果可能对OA早期演变过程中的某些患者具有重要的治疗意义。