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

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J Rheumatol 2002 Sep;29 Suppl 65:10-5

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

rheumatoid arthritis?

Dayer JM.

jean-michel.dayer@...

Much debate has focused on the relative importance of interleukin 1 (IL-1)

and tumor necrosis factor-a (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.

PMID: 12233836 [PubMed - in process]