Interleukin 1 or Tumor Necrosis Factor-a: Which Is the Real Target in Rheumatoid Arthritis?

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Interleukin 1 or Tumor Necrosis Factor-a: Which Is the Real Target in

Rheumatoid Arthritis?

JEAN-MICHEL DAYER

ABSTRACT.

Much debate has focused on the relative importance of interleukin 1

(IL-1) and tumor necrosis factor-a (TNF-a) 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-a overlap, they have somewhat differing roles in RA on the

basis of evidence from several animal models. TNF-a 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-a strongly synergize in

numerous biological functions, both in vitro and in vivo. Blockade of

IL-1 and TNF-a simultaneously provides favorable effects in collagen and

adjuvant induced arthritis, illustrating the importance of both

cytokines. (J Rheumatol 2002;29 Suppl 65:10-15)