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The Role of IL‐1 and IL‐1Ra in Joint Inflammation and Cartilage Degradation

2006; Elsevier BV; Linguagem: Inglês

10.1016/s0083-6729(06)74016-x

2162-2620

C. Jacques, Marjolaine Gosset, Françis Berenbaum, Cem Gabay,

Inflammasome and immune disorders

Interleukin (IL)‐1 is a cytokine that plays a major role in inflammatory responses in the context of infections and immune‐mediated diseases. IL‐1 refers to two different cytokines, termed IL‐1α and IL‐1β, produced from two genes. IL‐1α and IL‐1β are produced by different cell types following stimulation by bacterial products, cytokines, and immune complexes. Monocytes/macrophages are the primary source of IL‐1β. Both cytokines do not possess leader peptide sequences and do not follow a classical secretory pathway. IL‐1α is mainly cell associated, whereas IL‐1β can be released from activated cells after cleavage of its amino‐terminal region by caspase‐1. IL‐1 is present in the synovial tissue and fluids of patients with rheumatoid arthritis. Several in vitro studies have shown that IL‐1 stimulates the production of mediators such as prostaglandin E2, nitric oxide, cytokines, chemokines, and adhesion molecules that are involved in articular inflammation. Furthermore, IL‐1 stimulates the synthesis and activity of matrix metalloproteinases and other enzymes involved in cartilage destruction in rheumatoid arthritis and osteoarthritis. The effects of IL‐1 are inhibited in vitro and in vivo by natural inhibitors such as IL‐1 receptor antagonist and soluble receptors. IL‐1 receptor antagonist belongs to the IL‐1 family of cytokines and binds to IL‐1 receptors but does not induce any intracellular response. IL‐1 receptor antagonist inhibits the effect of IL‐1 by blocking its interaction with cell surface receptors. The use of IL‐1 inhibitors in experimental models of inflammatory arthritis and osteoarthritis has provided a strong support for the role of IL‐1 in the pathogeny of these diseases. Most importantly, these findings have been confirmed in clinical trials in patients with rheumatic diseases. Additional strategies aimed to block the effect of IL‐1 are tested in clinical trials.