Hein Gert E, Köhler Markus, Oelzner Peter, Stein Günter, Franke Sybille
Rheumatology and Osteology, Department of Internal Medicine III, Friedrich Schiller University of Jena, 07740 Jena, Germany.
Rheumatol Int. 2005 Dec;26(2):137-41. doi: 10.1007/s00296-004-0518-1. Epub 2004 Dec 3.
Oxidative stress and inflammatory processes accelerate the formation of advanced glycation end products (AGE), e.g. of pentosidine. The aim of this study was to investigate the relationships between levels of pentosidine in serum and synovial fluid, proinflammatory cytokines, other markers of inflammatory activity, and the state of radiologically visible bone destruction in patients with rheumatoid arthritis (RA).
One hundred thirty-three nondiabetic RA patients and 56 age-matched, healthy subjects were included. Serum and synovial fluid pentosidine, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and rheumatoid factor levels were determined. In 30 patients, the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and TNF-alpha and the soluble receptors sIL-2R, sIL-6R, sTNF-alpha, and RI/RII were also measured.
Serum levels of pentosidine were on average significantly higher in RA patients than in healthy subjects and correlated significantly to ESR, CRP, and serum levels of IL-6. Serum and synovial fluid pentosidine did not show any differences. Rheumatoid factor-positive RA patients had higher pentosidine levels in the synovial fluid than rheumatoid factor-negative patients. Correlations could not be found between pentosidine and the other cytokines or cytokine receptors measured.
The binding of AGE on cell receptors induces activation of nuclear factor kappa B, resulting in enhanced synthesis of proinflammatory cytokines. Moreover, AGE generation may also lead to the formation of new, immunologically relevant epitopes at synovial proteins. Both mechanisms could contribute to initiation and perpetuation of the inflammatory and destructive processes in RA.
氧化应激和炎症过程会加速晚期糖基化终产物（AGE）的形成，例如戊糖苷。本研究的目的是调查类风湿关节炎（RA）患者血清和滑液中戊糖苷水平、促炎细胞因子、炎症活动的其他标志物以及放射学可见骨破坏状态之间的关系。
纳入133例非糖尿病RA患者和56例年龄匹配的健康受试者。测定血清和滑液中的戊糖苷、红细胞沉降率（ESR）、C反应蛋白（CRP）和类风湿因子水平。在30例患者中，还检测了促炎细胞因子白细胞介素（IL）-1β、IL-6和肿瘤坏死因子-α以及可溶性受体sIL-2R、sIL-6R、sTNF-α和RI/RII。
RA患者血清中戊糖苷水平平均显著高于健康受试者，且与ESR、CRP和IL-6血清水平显著相关。血清和滑液中的戊糖苷无差异。类风湿因子阳性的RA患者滑液中戊糖苷水平高于类风湿因子阴性患者。未发现戊糖苷与所检测的其他细胞因子或细胞因子受体之间存在相关性。
AGE与细胞受体结合可诱导核因子κB活化，导致促炎细胞因子合成增加。此外，AGE的产生还可能导致滑膜蛋白上新的免疫相关表位形成。这两种机制都可能有助于RA炎症和破坏过程的启动和持续。
