Tumor necrosis factor a blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue
Tumor necrosis factor a blockade reduces the synovial cell infiltrate early after initiation of treatment, but apparently not by induction of apoptosis in synovial tissue
复制标题
DOI：
10.1002/art.11098
复制
发表时间：
2003-08-01
影响因子：
--
通讯作者：
Tak, PP
中科院分区：
文献类型：
--
作者：
Smeets, TJM;Kraan, MC;Tak, PP
客观的。为了确定用嵌合抗肿瘤坏死因子a抗体英夫利昔单抗治疗是否可以通过诱导滑膜组织中的细胞凋亡来减少细胞构成。方法。 24 名患有活动性疾病的类风湿性关节炎患者被随机分配接受静脉注射英夫利昔单抗 (3 mg/kg) (n = 12) 或安慰剂 (n = 12)。所有患者在开始治疗前均进行关节镜滑膜活检。第一次关节镜检查后 48 小时，对同一索引关节进行第二次关节镜滑膜活检。在第二次关节镜检查后，最初接受安慰剂的患者也在一项扩展研究中接受了英夫利昔单抗治疗。第 28 天对所有患者进行了第三次关节镜检查。进行免疫组织学分析以表征细胞浸润。采用TUNEL法和电子显微镜对凋亡细胞进行原位检测。结果。开始英夫利昔单抗治疗 48 小时后，内膜巨噬细胞数量显着减少；在安慰剂组中没有观察到这一点。在英夫利昔单抗治疗的患者中，亚衬巨噬细胞、T 细胞和浆细胞的数量也趋于减少，但在安慰剂组中则没有。有趣的是，我们没有检测到英夫利昔单抗治疗后凋亡细胞数量有任何增加。结论。英夫利昔单抗治疗可在开始治疗后 48 小时内减少类风湿滑膜组织中炎症细胞的数量，但显然不是通过诱导细胞凋亡来减少。可以想象，细胞浸润减少主要是由于细胞迁移的早期抑制所致。
Objective. To determine whether treatment with the chimeric anti-tumor necrosis factor a antibody infliximab could reduce cellularity by the induction of apoptosis in synovial tissue.Methods. Twenty-four rheumatoid arthritis patients with active disease were randomized to receive either infliximab (3 mg/kg) (n = 12) or placebo (n = 12) intravenously. All patients were subjected to arthroscopic synovial biopsy directly before initiation of treatment. A second arthroscopic synovial biopsy of the same index joint was performed 48 hours after the first arthroscopy. After the second arthroscopy, the patients who had initially received placebo were also treated with infliximab in an extension study. A third arthroscopy was performed in all patients on day 28. Immunohistologic analysis was performed to characterize the cell infiltrate. In situ detection of apoptotic cells was performed by TUNEL assay and electron microscopy.Results. At 48 hours after initiation of infliximab treatment, there was a significant reduction in the number of intimal macrophages; this was not observed in the placebo group. The number of sublining macrophages, T cells, and plasma cells also tended to be decreased in infliximab-treated patients, but not in the placebo group. Of interest, we did not detect any increase in the number of apoptotic cells after infliximab treatment.Conclusion. Infliximab therapy may reduce the number of inflammatory cells in rheumatoid synovial tissue as soon as 48 hours after initiation of treatment, but apparently not by induction of apoptosis. Conceivably, decreased cell infiltration primarily results from early inhibition of cell migration.