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Volume 3 Supplement 2

21st European Workshop for Rheumatology Research

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Adenoviral-based overexpression of TIMP-1 reduces tissue damage in the joints TNF-transgenic mice

  • 1,
  • 1,
  • 2,
  • 3,
  • 4,
  • 1, 3 and
  • 1, 3
Arthritis Research & Therapy20013 (Suppl 2) :P088

https://doi.org/10.1186/ar257

  • Received: 15 January 2001
  • Published:

Keywords

  • Rheumatoid Arthritis
  • Arthritis
  • Tissue Damage
  • Inflammatory Process
  • Systemic Treatment

Introduction

Rheumatoid arthritis is a prototype of a destructive inflammatory process. Inflammation triggered by the overexpression of TNF-a is recognized as a driving force of the disease process and mediated tissue destruction. The particular impact of TNF-a-dependent pathways in tissue destruction is unknown.

Materials and methods

Herein, the effect of an overexpression of tissue inhibitor of metalloproteinases (TIMP)-1, a physiological antagonist of metalloproteinases, was studied in the arthritis model of TNF-a-transgenic mice. Systemic treatment was carried out by replication defective adenoviral vectors for TIMP-1 (AdvTIMP1, n =7) or b-galactosidase (AdvLacZ, n = 6) or phosphate buffered saline (PBS, n = 7), which were injected once intravenously at the onset of arthritis. Clinical, serological, radiological and histological outcomes were assessed 18 days after treatment.

Results

The AdvTIMP1 group showed a significantly improved clinical outcome as measured by paw swelling and grip strength than the two control groups, whereas total body weight, TNF-a and IL-6 levels were similar in all groups. Tissue destruction as assessed by X-ray and histology of hind paws was significantly lower in the AdvTIMP1 group than in the AdvLacZ- and PBS- control groups. Finally, the formation of arthritis-specific autoantibodies to hnRNP-A2 was not observed in the AdvTIMP1 group but were present in the two control groups.

Discussion

These results indicates a central role of metalloproteinases in TNF-a-mediated tissue damage in vivo and a promising therapeutic role of TIMP-1.

Authors’ Affiliations

(1)
Division of Rheumatology, Department of Internal Medicine III, University of Vienna, Vienna
(2)
Institute for Biomedical Aging Research, Austrian Academy of Sciences, Innsbruck
(3)
Ludwig Boltzmann-Institute for Rheumatology and Balneology, Vienna, Austria
(4)
Department of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece

Copyright

© BioMed Central Ltd 2001

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