The Interleukin 1β Pathway in the Pathogenesis of Osteoarthritis

Osteoarthritis (OA) is a major disabling disease and is ranked as a major cause of chronic pain in adults. The pathology of the illness is characterized by a loss of articular cartilage leading to narrowing of joint space, increased joint friction, potential structural remodeling, persistent pain, and functional impairment. The proinflammatory cytokine interleukin 1 beta (IL-1 beta) has several chemical and bioactive characteristics allowing this catabolic protein to be involved in initiation and progression of OA. We review the current understanding of the pathogenesis of OA, and how upregulation of IL-1 beta initiates a cascade of intracellular events that can culminate in activation of proteinases,creation of a pro-destructive articular milieu, suppression of anabolic pathways, and a decrease in the synthesis of cartilage extracellular matrix. Therapeutic approaches to block the action of IL-1 beta and overcome its signal transduction to curtail disease progression are discussed. (First Release Oct 15 2008; J Rheumatol 2008;35:2306-12; doi: 10.3899/jrheum.080346)