TNF alpha and IL-1 beta are separate targets in chronic arthritis.
Chronic arthritis is characterized by persistent joint inflammation and concomitant joint destruction. Using murine arthritis models and neutralizing antibodies as well as cytokine-specific knockout conditions, it was found that tumor necrosis factor alpha (TNF alpha) is important in joint swelling, whereas a direct role in tissue destruction is unlikely. Interleukin-1 (IL-1) is not a dominant cytokine in early joint swelling, but has a pivotal role in sustained cell infiltration and erosive cartilage damage. TNF alpha-independent IL-1 production is a prominent feature in murine arthritis models, implying that IL-1 as well as TNF alpha are appropriate targets for therapy. These observations provide evidence for the potential uncoupling of joint inflammation and erosive changes and underline the need for TNF alpha/IL-1 directed combination-therapy approaches.
van den Berg
W B
WB
Department of Rheumatology, University Hospital Nijmegen, The Netherlands. w.vandenberg@reuma.azn.nl
Joosten
L A
LA
van de Loo
F A
FA
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D007375:Interleukin-1 / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha