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 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 10⁻⁷M 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 10⁻⁶M, 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.