Interleukin 1 or tumor necrosis factor-alpha: which is the real target in rheumatoid arthritis?
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.
Dayer
Jean-Michel
JM
Division of Immunology and Allergy, Geneva University Hospital, Switzerland. jean-michel.dayer@hcuge.ch
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000503:physiopathology*; D015415:Biomarkers / Q000032:analysis; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D015415:Biomarkers; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha