Role of interleukin 1 and interleukin 1 receptor antagonist in the mediation of rheumatoid arthritis

Chronic arthritis is characterised by chronic joint inflammation and concur rent joint erosion and destruction. The inflammatory cytokine interleukin 1 (IL1) has been shown to be a key mediator in the autoimmune disease rheuma toid arthritis (RA). Interleukin 1 mediates bone resorption and cartilage d estruction, but may not play as dominant a part in joint swelling and infla mmation. Interleukin 1 receptor antagonist (IL1Ra) selectively inhibits the effects of IL1 by competing for the IL1 receptor on all surfaces of the sy novium. In a randomised controlled trial in 472 patients with active diseas e, IL1Ra 30 mg/day, 75 mg/day or 150 mg/day given by subcutaneous injection significantly reduced the signs and symptoms of RA at 24 weeks. An America n College of Rheumatology (ACR) 20% response was seen in 43% of the patient s treated with 150 mg/day at 24 weeks. IL1Ra was well tolerated; injection site reactions were the most common adverse event. In another trial, in 419 patients with active RA treated concomitantly with methotrexate, there wer e ACR 20% responses after 24 weeks in 42% of the patients treated with 1 mg /kg/day by subcutaneous injection and in 35% of those treated with 2 mg/kg/ day. I1Ra offers a unique selective, targeted mechanism of action to block the IL1 mediated effects of RA.