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Uncoupling of inflammatory and destructive mechanisms in arthritis
1Department of Rheumatology, University Medical Center, Nijmegen, The Netherlands.
Objective:
To update clinicians on recent advances in the differentiation of the mechanisms of inflammation and cartilage destruction in the pathogenesis of rheumatoid arthritis (RA).
Methods:
We present analysis of recent published literature and abstracts that elucidates the independent actions of pivotal proinflammatory cytokines. These experimental data provide the framework for understanding the uncoupling of destructive and inflammatory mechanisms in arthritis.
Results:
Tumor necrosis factor-alpha (TNF-alpha) is an important mediator in the inflammation that occurs in RA. Interleukin-1 (IL-1) has a dominant effect on cartilage destruction that occurs later in the disease process. TNF-independent IL-1 production occurs in many RA model situations. Cytokine balance determines the erosive nature of the disease.
Conclusion:
IL-1 is at least as important as TNF-alpha in promoting the disease process. The pathways by which the inflammatory and destructive changes occur suggest that targeted anticytokine intervention will arrest the cartilage damage that occurs in patients with RA.