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Interleukin-1 (IL-1) and Interleukin-1 Receptor Antagonist (IL-1Ra)
It has been found that cytokines may play an important part in the pathogenesis of rheumatoid arthritis (RA).1 Production of cytokines is part of the immune system response to inflammation. Interleukin-1 (IL-1) is an inflammatory mediator that is produced in areas of inflammation. It binds to the IL-1 receptor type 1 (IL-1RI), which triggers the inflammatory response. The inflammation caused by RA triggers an increase in the production of cytokines, including IL-1, in the affected areas, which are characteristically located in the synovial tissue of the affected joint.2 In some cases, the increase in IL-1 production is such that it overwhelms the development of IL-1Ra (see Figure 1).3 Excessive levels of IL-1 in synovial tissue have been associated with greater attrition of bone and cartilage.4 The goal of the IL-1 receptor antagonist (IL-1Ra) is to help provide a balance against the destructive effects of an overabundance of IL-1.5,6
Overexpression of IL-1 Can Play a Prominent Role in the Pathogenesis of RA A study by Eastgate et al has demonstrated that patients with active RA have elevated levels of IL-1 (see Figure 2).8
Not all patients respond to anti-TNF Therapy. Tumor necrosis factor (TNF) is one of the key cytokines in the synovial inflammation process. Several anti-TNF agents have been developed for the treatment of RA. Initial studies suggested that TNF-α inhibition would reduce the production of other inflammatory mediators. Across clinical trials, however, there is still a small proportion of patients who did not achieve an American College of Rheumatology response criteria of 20 (ACR 20), therefore not all patients may have an adequate response.10-13 When TNF inhibition fails to adequately manage RA, patients may have IL-1 responsive disease. Potential indicators of IL-1 responsive RA may include breakthroughs in signs and symptoms despite increases in approved dosing of therapeutic agents, or less than an ACR 20 improvement after 3 to 5 month of anti-TNF therapy.14-16 When circumstances point to IL-1 responsive disease, IL-1 inhibition may offer patients significant benefits. Kineret® is a recombinant, nonglycosylated synthetic form of the human interleukin-1 receptor antagonist (IL-1Ra) that mimics the body's endogenous mechanism for regulating IL-1. Kineret® has a molecular weight of 17.3 kilodaltons and is comprised of 153 amino acids. The primary delineation between Kineret® and endogenous human IL-1Ra is the inclusion of a single methionine residue to the amino terminus of Kineret®. Kineret® is designed to mitigate the imbalance of IL-1.17 It works by competitively inhibiting IL-1 binding to the IL-1 receptor type 1 (IL-1Rl), thus inhibiting the biologic activity of IL-1 (see Figure 3). This process mimics the activity of endogenous IL-1Ra.18, 19
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ABOUT KINERET® ABOUT IL-1 PROFESSIONAL RESOURCES REIMBURSEMENT IMPORTANT PRODUCT SAFETY INFORMATION GLOSSARY |
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