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MR Vol.13 No.1 indexに戻る
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MODERN RHEUMATOLOGY
Vol.13 No.1 |
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The role of interleukin-1 receptor antagonist
in the prevention and treatment of disease |
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| W. P. Arend1 |
| (1)Division of Rheumatology, University of Colorado
Health Sciences Center B115, 4200 East Ninth Avenue, Denver, CO 80262,
USA |
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| Abstract |
| Abstract Interleukin-1 (IL-1) and tumor necrosis
factor ! (TNF-!) 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. |
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| Key words |
| Key words Cytokines ・ Interleukin-1 (IL-1) ・ IL-1 receptor antagonist
・ Rheumatoid arthritis (RA) |
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