A follow-up to

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A follow-up to "Anti-cytokine therapy in chronic destructive arthritis" by Wim B van den Berg

BioMed Central
Publication Date
Jan 01, 2001
  • Biology
  • Medicine


AR0304c04_Brennan.qxd IL = interleukin; IL-1ra = interleukin-1 receptor antagonist; RA = rheumatoid arthritis; TNF = tumour necrosis factor. Available online http://arthritis-research.com/content/3/4/211 In his review article [1], Professor van den Berg discusses anti-cytokine therapy of RA and hypothesises that, in order to prevent joint destruction, it is necessary to block IL-1 in addition to TNF. The rationale for this hypothesis stems largely from observations in experimental models of arthri- tis in rodents. However, as he points out in the abstract, the necessity arises “if elements of the models apply to the arthritic process in RA patients”. This surely is the central point, and the critical question is whether animal models resemble the human disease process. This issue has been extensively debated and even in the best-defined models, such as collagen-induced arthritis in DBA/1 mice, the aggressive, acute nature of the disease makes it unlike human RA. The very lack of chronicity in experimental models is a major limitation. Although these models and cytokine transgenic mice, despite their drawbacks, have been an invaluable tool to test hypotheses in vivo and to further explore mechanisms in a real-life setting, they can never fully mimic human RA. Perhaps one of the best-studied models illustrating the problem of extrapolation from animal models to human disease is one in the huTNF transgenic mouse developed by Kollias and colleagues a decade ago. Replacement with 3′UTR of β-globin of the normal regulatory untrans- lated region in the TNF gene resulted in chronic arthritis in the Tg 197 line; the development of this arthritis was specifically blocked by antihuman, but not antimouse, TNF-α antibodies [2]. However, what is clearly important (even central) to the development of arthritis in these mice is the fact that the trans gene is expressed as protein in the synovial fibroblasts [3]. Normal fibroblasts, while having the capability to make TNF mRNA, block the trans- lation proce

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