Cope A P, Aderka D, Doherty M, Engelmann H, Gibbons D, Jones A C, Brennan F M, Maini R N, Wallach D, Feldmann M
Mathilda and Terence Kennedy Institute of Rheumatology, Bute Gardens and Sunley Research Centre, London, UK.
Arthritis Rheum. 1992 Oct;35(10):1160-9. doi: 10.1002/art.1780351008.
Recently, 2 classes of cytokine inhibitors have been defined at the molecular level. The largest group comprises the extracellular domains of cell surface cytokine receptors, and includes both tumor necrosis factor receptors (TNF-R). The present study was conducted to investigate the role of TNF inhibitors in arthritis.
We measured p55 and p75 soluble TNF-R (sTNF-R) in serum and synovial fluid (SF) samples from patients with rheumatic diseases and compared their levels with levels of soluble interleukin-2 receptors (sIL-2R). Sensitive enzyme-linked immunosorbent assays (ELISA), specific for p55 and p75 sTNF-R and for sIL-2R, were used.
Serum levels of p75 sTNF-R were 3-4-fold higher than levels of p55 sTNF-R, and both were significantly elevated in patients with osteoarthritis (OA) and rheumatoid arthritis (RA) compared with healthy controls. RA SF levels of sTNF-R were 4-5-fold higher than levels in serum, suggesting local production in the joint, and were significantly higher than levels in the SF of patients with seronegative arthropathy or OA. Furthermore, levels of p55 and p75 sTNF-R, but not sIL-2R or TNF alpha measured by ELISA, were increased in the SF of patients with clinically active RA. The soluble TNF-R in RA and OA SF were functional since they inhibited TNF activity in a cytotoxicity assay in proportion to the levels of inhibitor present. Evaluation of serially obtained serum samples suggested that sTNF-R may be a useful parameter for monitoring RA disease activity.
Biologically active soluble TNF-R are up-regulated in patients with rheumatic disease and are produced locally in the joints. Measurement of serum levels of TNF-R may be useful for monitoring of disease, and determination of SF levels could be of diagnostic value.
最近，在分子水平上定义了两类细胞因子抑制剂。最大的一组包括细胞表面细胞因子受体的胞外结构域，其中包括肿瘤坏死因子受体（TNF-R）。本研究旨在探讨TNF抑制剂在关节炎中的作用。
我们测量了风湿性疾病患者血清和滑液（SF）样本中的p55和p75可溶性TNF-R（sTNF-R），并将其水平与可溶性白细胞介素-2受体（sIL-2R）的水平进行比较。使用了对p55和p75 sTNF-R以及sIL-2R具有特异性的灵敏酶联免疫吸附测定（ELISA）。
p75 sTNF-R的血清水平比p55 sTNF-R的水平高3至4倍，与健康对照组相比，骨关节炎（OA）和类风湿关节炎（RA）患者的这两者水平均显著升高。RA患者SF中sTNF-R的水平比血清中的水平高4至5倍，表明在关节中局部产生，并且显著高于血清阴性关节病或OA患者的SF中的水平。此外，在临床活动期RA患者的SF中，通过ELISA测量的p55和p75 sTNF-R的水平升高，但sIL-2R或TNFα的水平未升高。RA和OA患者SF中的可溶性TNF-R具有功能，因为它们在细胞毒性试验中按存在的抑制剂水平比例抑制TNF活性。对连续获取的血清样本的评估表明，sTNF-R可能是监测RA疾病活动的有用参数。
生物活性可溶性TNF-R在风湿性疾病患者中上调，并在关节局部产生。测量血清中TNF-R的水平可能有助于疾病监测，而测定SF水平可能具有诊断价值。
