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Semin Arthritis Rheum. 2001 Apr;30(5 Suppl 2):1-6.

Cytokine imbalance in the pathogenesis of rheumatoid arthritis: the role of interleukin-1 receptor antagonist.

Author information

  • University of Colorado Health Sciences Center, Denver, CO 80262, USA.

Abstract

OBJECTIVES:

To summarize the role of cytokine imbalance in the pathogenesis of rheumatoid arthritis.

METHODS:

The literature on cytokines in rheumatoid arthritis from American and European medical journals was reviewed.

RESULTS:

An important role of interleukin (IL)-1 and tumor necrosis factor (TNF)-alpha in the mediation of tissue damage in the rheumatoid joint has been well established over the past 10 years. The IL-1 family consists of 2 agonists, IL-1alpha and IL-1beta, and a specific naturally occurring receptor antagonist, IL-1Ra. Both forms of IL-1 induce intracellular responses through binding to the type 1 IL-1 receptor (IL-1R) on target cells. IL-1Ra binds to IL-1R with an avidity equal to that of IL-1 but fails to stimulate the cells, thus functioning as an inhibitor of IL-1 binding. Endogenous production of IL-1Ra is an important anti-inflammatory mechanism both in animal models of disease and in human disease. In the rheumatoid synovium, an imbalance exists in this system, because the relative levels of production of IL-1Ra are not adequate to effectively block the proinflammatory effects of IL-1. Studies in different animal models of inflammatory arthritis indicate that a deficiency of IL-1Ra relative to IL-1 leads to more severe disease and even to the spontaneous development of arthritis as observed in IL-1Ra knockout mice. A restoration of the balance between IL-1Ra and IL-1 in human disease can theoretically be achieved through the administration of recombinant IL-1ra protein, gene therapy with the IL-1Ra complementary DNA, or stimulation of production of endogenous IL-1Ra.

CONCLUSIONS:

An imbalance between proinflammatory cytokines and cytokine antagonists or inhibitors may be one factor predisposing to initiation or perpetuation of rheumatoid synovitis.

Copyright 2001 by W.B. Saunders Company.

PMID:
11357165
[PubMed - indexed for MEDLINE]
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