TNFa and IL-1b are separate targets in chronic arthritis

W.B. van den Berg, L.A.B. Joosten, F.A.J. van de Loo

Department of Rheumatology, University Hospital Nijmegen, The Netherlands.

ABSTRACT
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 a (TNFa) 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. TNFa-independent IL-1 production is a prominent feature in murine arthritis models, implying that IL-1 as well as TNFa are appropriate targets for therapy. These observations provide evidence for the potential uncoupling of joint inflammation and erosive changes and underline the need for TNFa/IL-1 directed combination-therapy approaches.

Key words
Cartilage destruction, chronic inflammation, anti-cytokine therapy.

Please address correspondence and reprint requests to: Prof. Wim B. van den Berg, Department of Rheumatology, University Hospital Nijmegen, Geert Grooteplein Zuid 8, 6500 HB Nijmegen, The Netherlands.
E-mail: w.vandenberg@reuma.azn.nl

Clin Exp Rheumatol 1999; 17 (Suppl. 18): S105 - S114.
© Copyright Clinical and Experimental Rheumatology 1999.