Induction of neutrophil‐mediated cartilage degradation by interleukin‐8

Abstract 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 35 S‐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.