Interferon-gamma increases human neutrophil-mediated cartilage proteoglycan degradation

Interferon gamma (IFN-gamma) is known to activate neutrophils and is produced by the synoviocytes, macrophages, T cells and other inflammatory cells in rheumatoid arthritis. Neutrophils participate in articular cartilage destruction and predominate in the synovial fluid of inflamed joints during the early stages and acute exacerbations of the disease. In this study we investigated the effect of recombinant human IFN-gamma on human neutrophil damage to bovine articular cartilage explants which had been coated with heat-aggregated IgG (HAGG). Cartilage proteoglycan degradation by neutrophils was augmented by IFN-gamma at 10(2)-10(4) U/ml. IFN-gamma also increased neutrophil-mediated proteoglycan degradation when the cells were preincubated with IFN-gamma and washed before addition to cartilage. This activity of IFN-gamma was abolished by boiling and was unaffected by polymixin B, indicating that the effects of IFN-gamma were not due to endotoxin contamination. In the absence of neutrophils IFN-gamma had no effect on proteoglycan metabolism, and the ability of IFN-gamma to increase neutrophil-mediated proteoglycan degradation did not require living chondrocytes. Adherence of neutrophils to HAGG-coated and uncoated cartilage explants was enhanced by IFN-gamma. Opsonisation of the cartilage with HAGG also increased the adhesion of neutrophils. In contrast to the enhancement of neutrophil-mediated proteoglycan degradation, IFN-gamma had no effect on the inhibition of proteoglycan synthesis by neutrophils.