[Importance of interleukin-I receptors in osteoarthritis]

Osteoarthritis (OA) is a degenerative disease of the articular cartilage associated with a variable degree of synovial inflammation which appears to play an important role in the pathophysiological process by interacting with and thereby accelerating catabolism. Interleukin-1 (IL-1) is a main contributor to these changes. Its action is mediated via binding to specific receptors on target cells. In human cells, two types of IL-1 receptors (IL-1R) have been characterized: the type I and the type II. Extensive characterization of IL-1R on both chondrocytes and synoviocytes demonstrated that the type I is predominant. Recent data suggested the importance of these receptors in OA pathophysiology. A two-fold increase in the number of sites per cell was found in OA cells, which resulted in a higher sensitivity of the latter cell to stimulation by IL-1. Understanding the elements involved in the regulation of these receptors will, therefore, provide a better insight for therapeutic strategy. Findings regarding IL-1 inhibitors, such as soluble IL-1R (sIL-1R) and IL-1 receptor antagonist (IL-1ra) offer exciting possibilities for controlling cytokine biology. Recent investigation of the IL-1ra system by our laboratory has explored its role in OA. Results from two studies will be discussed.