Arguments for interleukin 1 as a target in chronic arthritis.
Tumour necrosis factor (TNF) and interleukin 1 (IL1) are considered as master cytokines in chronic, destructive arthritis. Therapeutic approaches in rheumatic arthritis (RA) patients so far mainly focused on TNF. Although TNF is a major inflammatory mediator in RA and a potent inducer of IL1, anti-TNF treatment is not effective in all patients, nor does it fully control the arthritic process in affected joints of good responders. Analysis of cytokine patterns in early synovial biopsy specimens of RA patients reveals prominent TNF staining in 50% of the patients, whereas IL1b staining was evident in 100%. This argues that TNF independent IL1 production occurs in some of the patients. Studies in a range of experimental arthritis models in mice make it clear that TNF is involved in early joint swelling. However, TNF alone is not arthritogenic nor destructive and exerts its arthritogenic potential through IL1 induction. Intriguingly, TNF independent IL1 production is found in many models. Its relevance is further underlined by the greater efficacy of anti-IL1 treatment as compared with anti-TNF treatment and the total lack of chronic, erosive arthritis in IL1b deficient mice. IL1b is not necessarily involved in early joint swelling, but is a crucial mediator in chronic arthritis and cartilage erosion in all models studied so far. This makes ILb an attractive target in chronic, destructive arthritis.
van den Berg
W B
WB
Department of Rheumatology, University Medical Centre St Radboud, Nijmegen, the Netherlands. w.vandenberg@reuma.azn.nl
D000818:Animals; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D001862:Bone Resorption / Q000503:physiopathology; D002358:Cartilage, Articular / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha