Overexpression of TNF causes bilateral sacroiliitis

To study the role of TNF in sacroiliitis using a TNF-α transgenic (hTNFtg) mouse model.

hTNFtg mice were divided into two groups receiving either phosphate-buffered saline (PBS) or anti-TNF (infliximab). Wild-type mice served as negative control. Treatment was initiated at week 4 and continued over 6 weeks. Thereafter the sacroiliic joints were histologically assessed for joints inflammation, local bone erosion and cartilage destruction.

All hTNFtg mice showed a severe bilateral sacroiliitis. Treatment of hTNFtg mice with anti-TNF, however, resulted in a significant (P < 0.05), over 80% reduction in sacroiliacal inflammation. Furthermore, in hTNFtg mice severe erosions of the iliac as well as sacral sub-chondral bones were detectable, whereas treatment with anti-TNF virtually abrogated local bone erosions indicated by a reduction by over 99%. In addition, application of anti-TNF also significantly (P < 0.05) reduced the numbers of osteoclasts at the front of erosions by 98% compared with PBS-treated hTNFtg mice. The amount of sacroiliac cartilage of hTNFtg mice was significantly (P < 0.05) reduced by 73% compared with anti-TNF treated mice.

These data clearly indicate that TNF overexpression causes bilateral, erosive sacroiliitis and that anti-TNF therapy is a suitable tool with which to treat this condition.

Affiliations

1. Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Austria

   • K Redlich
   • , B Görtz
   • , S Hayer
   • , J Zwerina
   • , G Steiner
   • , JS Smolen
   •  & G Schett

2. Molecular Genetics Laboratory, Institute of Immunology, Alexander Fleming Biomedical Sciences Research Center, Vari, Greece

   • G Kollias

3. Center of Molecular Medicine, Austrian Academy of Sciences, Vienna, Austria

   • G Steiner
   •  & JS Smolen

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