The role of interleukin-1 receptor antagonist in the prevention and treatment of disease |
| |
Authors: | W P Arend |
| |
Institution: | (1) Division of Rheumatology, University of Colorado Health Sciences Center B115, 4200 East Ninth Avenue, Denver, CO 80262, USA Tel. +1-303-315-6666; Fax +1-303-315-5540 e-mail: william.arend@uchsc.edu, US |
| |
Abstract: | Interleukin-1 (IL-1) and tumor necrosis factor α (TNF-α) play key proinflammatory roles in a variety of human diseases, including
rheumatoid arthritis (RA). IL-1 receptor antagonist (IL-1Ra) is a naturally occurring structural variant of IL-1 that competitively
inhibits receptor binding of IL-1. Four forms of IL-1Ra have been described: secretory IL-1Ra (sIL-1Ra) and three intracellular
molecules (icIL-1Ra1, 2, and 3). Excess amounts of IL-1Ra are necessary to inhibit the biological effects of IL-1. The endogenous
production of IL-1Ra plays an anti-inflammatory role, but the level of production of IL-1Ra in inflamed tissues may not be
adequate to block IL-1 effectively. An allelic polymorphism in the IL-1Ra gene is associated with a variety of human diseases,
largely of epithelial or endothelial cell origin. The disease associated allele IL1RN*2 may lead to a decreased production of icIL-1Ra1 by these cells, predisposing the patient to an imbalance in the IL-1 system.
The therapeutic administration of IL-1Ra was found to be safe and efficacious in the treatment of RA. Intraarticular delivery
of the IL-1Ra cDNA by ex vivo gene therapy in patients with RA was effective in enhancing local IL-1Ra production. This unique
form of therapy is under further evaluation.
Correspondence to:W.P. Arend |
| |
Keywords: | Cytokines Interleukin-1 (IL-1) IL-1 receptor antagonist Rheumatoid arthritis (RA) |
本文献已被 SpringerLink 等数据库收录! |
|