Regulation of interleukin 1 receptors in human articular chondrocytes

Interleukin 1 (IL-1) exerts pronounced effects on articular cartilage by increasing matrix molecule turnover and metalloprotease synthesis. These effects are believed to be mediated through a high affinity cell surface receptor (IL-1R) present on chondrocytes. Normal human chondrocytes express about 3,000-5,000 sites/cell. The downregulation of IL-1R could potentially reduce the biological effectiveness of IL-1 and as a result influence inflammatory conditions. Agents which modulate the number of IL-1R were investigated. Cytokines, such as IL-1 alpha (1 ng/ml) and IL-1 beta (1 ng/ml), were found to reduce the chondrocyte IL-1R level by about 78% versus the control. Other cytokines tested, IL-2 (20 ng/ml) and tumor necrosis factor-alpha (1 ng/ml), also reduced IL-1R levels but to a lesser extent; 52 and 69% inhibition were recorded, respectively. The growth factor bFGF (50 ng/ml) induced a 48% reduction versus the basal level, and a therapeutic dosage of indomethacin (1.5 micrograms/ml) elicited only a slight reduction (10%). Hydrocortisone had a variable effect on the IL-1R level.