Role of tumour necrosis factor alpha in experimental arthritis: separate activity of interleukin 1beta in chronicity and cartilage destruction.
Chronic arthritis is characterised by persistent joint inflammation and concomitant joint destruction. Using murine arthritis models and neutralising antibodies as well as cytokine specific knockout conditions, it was found that tumour necrosis factor alpha (TNFalpha) is important in early joint swelling. Membrane bound TNFalpha is sufficient to drive this aspect of inflammation as well as the acute cellular infiltrate in the synovial tissue. Interleukin 1 (IL1) is not necessarily a dominant cytokine in early joint swelling, but has a pivotal role in sustained cellular infiltration and erosive cartilage damage. TNFalpha independent IL1 production is a prominent feature in murine arthritis models. These observations provide evidence for potential uncoupling of joint inflammation and erosive changes, implying that both cytokines need to be targeted to achieve optimal treatment.
van den Berg
W B
WB
Department of Rheumatology, University Hospital Nijmegen, the Netherlands.
Joosten
L A
LA
Kollias
G
G
van De Loo
F A
FA
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001168:Arthritis / Q000276:immunology*; D002358:Cartilage, Articular / Q000276:immunology; D002908:Chronic Disease; D003094:Collagen; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000276:immunology*; D051379:Mice; D013291:Streptococcus / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000942:Antigens, Bacterial; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D003094:Collagen