Hardingham T E, Rayan V, Lewthwaite J C
Kennedy Institute of Rheumatology, Hammersmith, London, United Kingdom.
Rev Rhum Ed Fr. 1994 Nov 15;61(9 Pt 2):93S-98S.
Articular cartilage has important load bearing properties. These depend on the integrity of its matrix which is formed by a dense network of collagen fibres (mainly type II) and a high concentration of proteglycan (mainly aggrecan). The matrix is maintained by the chondrocytes, which control the production and turnover of matrix components and are greatly affected by cytokines (such as IL-1 alpha,beta and TNF alpha) and growth factors (such as IGF-1 alpha, beta TGF beta). They have strongly antagonistic effects. IL-1 alpha, beta and TNF alpha inhibit proteoglycan synthesis and at slightly higher concentration they enhance the rates of matrix degradation. In contrast the growth factor IGF-1 stimulates proteoglycan biosynthesis and reduces matrix proteinase action. TGB beta has less direct anabolic effect on matrix biosynthesis in normal cartilage, but does not induce an anabolic response in isolated chondrocytes or in explants following IL-1 treatment. We have also investigated the action of IL-1 in inflammatory arthritis in vivo by treatment with IL-1 receptor antagonist, the natural IL-1 inhibitor. In antigen-induced arthritis the effects of the injection of rh IL-1 ra was measured over 3 days. There was little effect on the induction of joint swelling, cellular infiltration into synovium or cartilage proteoglycan depletion, but when given over a similar time in more chronic arthritis, 14 days after induction it had a major effect on suppressing synovial fibrosis although it still did not affect parameters of joint inflammation. The results suggested that IL-1 was not the major factor inducing inflammation in the joint, but was responsible for the excessive collagen deposition in the synovium in this experimental model of arthritis.
关节软骨具有重要的承重特性。这些特性取决于其基质的完整性，该基质由密集的胶原纤维网络（主要是II型）和高浓度的蛋白聚糖（主要是聚集蛋白聚糖）构成。基质由软骨细胞维持，软骨细胞控制着基质成分的产生和周转，并受到细胞因子（如白细胞介素-1α、β和肿瘤坏死因子α）和生长因子（如胰岛素样生长因子-1α、β和转化生长因子β）的极大影响。它们具有强烈的拮抗作用。白细胞介素-1α、β和肿瘤坏死因子α抑制蛋白聚糖合成，在略高浓度时会提高基质降解速率。相反，生长因子胰岛素样生长因子-1刺激蛋白聚糖生物合成并降低基质蛋白酶活性。转化生长因子β对正常软骨中的基质生物合成的直接合成代谢作用较小，但在白细胞介素-1处理后的分离软骨细胞或外植体中不会诱导合成代谢反应。我们还通过用白细胞介素-1受体拮抗剂（天然的白细胞介素-1抑制剂）治疗，研究了白细胞介素-1在体内炎症性关节炎中的作用。在抗原诱导的关节炎中，在3天内测量了注射重组人白细胞介素-1受体拮抗剂的效果。对关节肿胀的诱导、细胞浸润到滑膜或软骨蛋白聚糖耗竭几乎没有影响，但在更慢性的关节炎中，在诱导后14天给予时，它对抑制滑膜纤维化有主要作用，尽管它仍然不影响关节炎症参数。结果表明，白细胞介素-1不是诱导关节炎症的主要因素，但在这个关节炎实验模型中，它是滑膜中胶原蛋白过度沉积的原因。
