Interleukin 1 or tumor necrosis factor-alpha: which is the real target in rheumatoid arthritis?

JM Dayer - The Journal of rheumatology Supplement, 2002 - jrheum.org
JM Dayer
The Journal of rheumatology Supplement, 2002jrheum.org
Much debate has focused on the relative importance of interleukin 1 (IL-1) and tumor
necrosis factor-alpha (TNF-alpha) in the pathophysiology of rheumatoid arthritis (RA). The
production of these cytokines by synovial macrophages is tightly regulated by cell-cell
contact with T cells. During this contact, several surface molecules are implicated in contact
mediated cytokine production, including CD40 ligand, CD11b/c, and CD69. Apolipoprotein
AI, an acute phase reactant (APR) that declines during systemic inflammation (reverse APR) …
Much debate has focused on the relative importance of interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) in the pathophysiology of rheumatoid arthritis (RA). The production of these cytokines by synovial macrophages is tightly regulated by cell-cell contact with T cells. During this contact, several surface molecules are implicated in contact mediated cytokine production, including CD40 ligand, CD11b/c, and CD69. Apolipoprotein A-I, an acute phase reactant (APR) that declines during systemic inflammation (reverse APR), inhibits cytokine production by interfering in the T cell-monocyte interaction. Although the effects of IL-1 and TNF-alpha overlap, they have somewhat differing roles in RA on the basis of evidence from several animal models. TNF-alpha appears to play a more important role in triggering events leading to inflammation both locally and systemically, whereas IL-1 is more involved at the local level in processes leading to cartilage and bone destruction and in impeding cartilage repair. However, IL-1 and TNF-alpha strongly synergize in numerous biological functions, both in vitro and in vivo. Blockade of IL-1 and TNF-alpha simultaneously provides favorable effects in collagen and adjuvant induced arthritis, illustrating the importance of both cytokines.
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