Goldring S R
Harvard Medical School, New England Baptist Bone and Joint Institute, Boston, MA, USA.
Rheumatology (Oxford). 2003 May;42 Suppl 2:ii11-6. doi: 10.1093/rheumatology/keg327.
Proinflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha), have been implicated in the dysregulation of bone and cartilage remodelling characteristic of rheumatoid arthritis (RA). With respect to bone remodelling, both of these cytokines have been shown to up-regulate the production of the receptor activator of nuclear factor-kappaB ligand, which acts to enhance osteoclastic bone resorption. TNFalpha stimulates differentiation of osteoclast progenitors into mature osteoclasts and IL-1 acts directly on osteoclasts to increase the bone-resorbing capacity of these cells. IL-1 and TNFalpha also adversely affect cartilage remodelling, although IL-1 is more potent on a molar basis. This cytokine not only increases production of factors that stimulate cartilage matrix degradation, but also inhibits the synthesis of type II collagen and proteoglycans. Enhanced understanding of the mechanisms underlying the processes of joint destruction will allow more selective and specific application of therapeutic agents that target these proinflammatory cytokines and, thus, more effective management of patients with RA and other inflammatory disorders.
促炎细胞因子，如白细胞介素-1（IL-1）和肿瘤坏死因子α（TNFα），被认为与类风湿性关节炎（RA）特有的骨和软骨重塑失调有关。关于骨重塑，这两种细胞因子均已显示出上调核因子κB受体活化因子配体的产生，该配体可增强破骨细胞的骨吸收。TNFα刺激破骨细胞祖细胞分化为成熟破骨细胞，而IL-1直接作用于破骨细胞以增加这些细胞的骨吸收能力。IL-1和TNFα也对软骨重塑产生不利影响，尽管按摩尔计算IL-1的作用更强。这种细胞因子不仅增加刺激软骨基质降解的因子的产生，还抑制II型胶原蛋白和蛋白聚糖的合成。对关节破坏过程潜在机制的深入了解将使针对这些促炎细胞因子的治疗药物能够更具选择性和特异性地应用，从而更有效地治疗RA和其他炎症性疾病患者。
