Elford P R, Cooper P H
Department of Endocrinology, Sandoz Research Institute Berne Ltd., Switzerland.
Arthritis Rheum. 1991 Mar;34(3):325-32. doi: 10.1002/art.1780340310.
Neutrophil influx into the inflamed joint is a characteristic feature of disease flares in patients with rheumatoid arthritis. Recently, a protein produced by monocytes and fibroblasts that has chemoattractive/activating properties for neutrophils has been identified and characterized. This protein has been called interleukin-8 (IL-8). In this study, we cocultured neutrophils with 35S-sulfate-labeled cartilage and found that the addition of recombinant human IL-8 (rHuIL-8) caused rapid, neutrophil-mediated cartilage degradation that was the result of induction of neutrophil degranulation by the cytokine. With 10(-7)M rHuIL-8, 23% of the radiolabel was released into the culture medium in 4 hours, compared with a 9% release without the factor. At concentrations of up to 10(-6)M, rHuIL-8 had no direct effect upon cartilage breakdown. These findings indicate that IL-8 may participate in the pathogenesis of rheumatoid arthritis through the induction of neutrophil-mediated cartilage damage.
中性粒细胞流入炎症关节是类风湿关节炎患者疾病发作的一个特征性表现。最近，一种由单核细胞和成纤维细胞产生的、对中性粒细胞具有趋化/激活特性的蛋白质已被鉴定和表征。这种蛋白质被称为白细胞介素-8（IL-8）。在本研究中，我们将中性粒细胞与35S-硫酸盐标记的软骨共培养，发现添加重组人IL-8（rHuIL-8）会导致快速的、中性粒细胞介导的软骨降解，这是细胞因子诱导中性粒细胞脱颗粒的结果。使用10^(-7)M的rHuIL-8，4小时内23%的放射性标记物释放到培养基中，而在没有该因子的情况下释放率为9%。在高达10^(-6)M的浓度下，rHuIL-8对软骨破坏没有直接影响。这些发现表明，IL-8可能通过诱导中性粒细胞介导的软骨损伤参与类风湿关节炎的发病机制。
