The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis.

The role of the cytokine network in mediating inflammation and joint destruction in rheumatoid arthritis (RA) has been investigated extensively in recent years. Interleukin-1 (IL-1) and tumour necrosis factor alpha (TNFalpha) are two pivotal proinflammatory cytokines that have been shown to contribute to the clinical manifestations of RA. The ability of IL-1 to drive inflammation and joint erosion and to inhibit tissue repair processes has been clearly established in in vitro systems and animal models. Under physiological conditions, the activity of IL-1 is balanced by IL-1 receptor antagonist (IL-1R alpha). Understanding of the respective roles of IL-1 and IL-1R alpha in conditions of health and disease has led to the development of a recombinant IL-1ra, anakinra (Kineret; Amgen Inc., Thousand Oaks, CA), which offers a new therapeutic modality for RA.