af Klint Erik, Grundtman Cecilia, Engström Marianne, Catrina Anca Irinel, Makrygiannakis Dimitrios, Klareskog Lars, Andersson Ulf, Ulfgren Ann-Kristin
Karolinska Institutet, Stockholm, Sweden.
Arthritis Rheum. 2005 Dec;52(12):3880-9. doi: 10.1002/art.21488.
To investigate whether intraarticular (IA) glucocorticoid (GC) therapy diminishes synovial cell infiltration, vascularity, expression of proinflammatory cytokines, and adhesion molecule levels in patients with chronic arthritides.
Thirty-one patients with chronic arthritides received a single IA injection of triamcinolone hexacetonide to treat active large-joint inflammation. Synovial biopsy specimens were obtained with arthroscopic guidance before and 9-15 days after injection. The presence of T lymphocytes, macrophages, intercellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), the pan-endothelial marker CD31, and the proinflammatory cytokines interleukin-1alpha (IL-1alpha), IL-1beta, tumor necrosis factor (TNF), and high mobility group box chromosomal protein 1 (HMGB-1) was studied by immunohistochemistry and real-time reverse transcriptase-polymerase chain reaction.
IA GC treatment resulted in good clinical response in 29 of 31 joints. After therapeutic intervention, the number of synovial T lymphocytes declined, whereas the number of macrophages remained unchanged. Overall synovial protein expression of TNF, IL-1beta, extranuclear HMGB-1, VEGF, and ICAM-1 was reduced at followup tissue sampling, while no significant effects were observed regarding vascularity. In contrast, expression of IL-1alpha, VEGF, and cytoplasmic HMGB-1 protein in vascular endothelial cells was not affected. GC therapy down-regulated levels of messenger RNA encoding IL-1alpha and IL-1beta, but not TNF or HMGB-1.
Synovial cell infiltration and proinflammatory cytokine expression were affected in a multifaceted manner by IA GC treatment. Marked reduction of synovial T lymphocytes, TNF, IL-1beta, extranuclear HMGB-1, ICAM-1, and VEGF occurred in association with beneficial clinical effects. Unexpectedly, macrophage infiltration and proinflammatory endothelial cytokine expression remained unchanged. These findings may reflect mechanisms controlling the transiency of clinical improvement frequently observed after IA GC injection.
探讨关节内（IA）糖皮质激素（GC）治疗是否能减少慢性关节炎患者的滑膜细胞浸润、血管生成、促炎细胞因子表达及黏附分子水平。
31例慢性关节炎患者接受单次关节内注射己曲安奈德以治疗活动性大关节炎症。在注射前及注射后9 - 15天，于关节镜引导下获取滑膜活检标本。通过免疫组织化学和实时逆转录聚合酶链反应研究T淋巴细胞、巨噬细胞、细胞间黏附分子1（ICAM - 1）、血管内皮生长因子（VEGF）、全内皮标志物CD31以及促炎细胞因子白细胞介素 - 1α（IL - 1α）、IL - 1β、肿瘤坏死因子（TNF）和高迁移率族蛋白B1（HMGB - 1）的存在情况。
IA GC治疗使31个关节中的29个获得了良好的临床反应。治疗干预后，滑膜T淋巴细胞数量减少，而巨噬细胞数量保持不变。在随访组织采样时，滑膜中TNF、IL - 1β、核外HMGB - 1、VEGF和ICAM - 1的总体蛋白表达降低，而血管生成方面未观察到显著影响。相反，血管内皮细胞中IL - 1α、VEGF和细胞质HMGB - 1蛋白的表达未受影响。GC治疗下调了编码IL - 1α和IL - 1β的信使核糖核酸水平，但未下调TNF或HMGB - 1的水平。
IA GC治疗以多方面方式影响滑膜细胞浸润和促炎细胞因子表达。滑膜T淋巴细胞、TNF、IL - 1β、核外HMGB - 1、ICAM - 1和VEGF的显著减少与有益的临床效果相关。出乎意料的是，巨噬细胞浸润和促炎内皮细胞因子表达保持不变。这些发现可能反映了控制IA GC注射后常见临床改善短暂性的机制。
