Induction of neutrophil-mediated cartilage degradation by interleukin-8.
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.
Elford
P R
PR
Department of Endocrinology, Sandoz Research Institute Berne Ltd., Switzerland.
Cooper
P H
PH
D000818:Animals; D002356:Cartilage / Q000473:pathology*; D002417:Cattle; D015550:Cell Degranulation; D002478:Cells, Cultured; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014155:Transcobalamins / Q000378:metabolism
D016209:Interleukin-8; D011994:Recombinant Proteins; D014155:Transcobalamins; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D005966:Glucuronidase