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  • Meeting abstract
  • Open Access

IL-22 gene transfer in collagen-induced arthritis

  • 1,
  • 2,
  • 3,
  • 1,
  • 3,
  • 1,
  • 1,
  • 2,
  • 1, 2, 3, 4 and
  • 1, 2, 3, 4
Arthritis Res Ther20046 (Suppl 1) :81

https://doi.org/10.1186/ar1123

  • Received: 16 January 2004
  • Published:

Keywords

  • Rheumatoid Arthritis
  • Gene Transfer
  • Amino Acid Identity
  • Adenoviral Vector
  • Synovial Fibroblast

Background and Objective

Novel cytokines have been identified by structural homology to IL-10. Among them, IL-22 showed a 25% amino acid identity with IL-10 and shared a common receptor β-subunit. The expression profile suggested involvement in the immune response in vivo. The present work evaluates the role of IL-22 in arthritis, examining the effects of systemic murine IL-22 adenoviral-mediated overexpression (Ad-mIL-22) in the collagen-induced arthritis (CIA) DBA1 mouse model.

Method

Human rheumatoid arthritis (RA) synovial fibroblast (SF) were infected in vitro with increasing doses of Ad-mIL-22 (0–25 MOI). Cytokine secretion was assessed in supernatant using a specific ELISA. Therapeutic efficiency of mIL-22 overexpression achieved by intravenous injection of Ad-mIL22 (5 × 109 pfu) after the onset of CIA was assessed. A group injected with a nonrelevant adenoviral vector (Ad-LacZ) was used as a control. Radiological and histological analyses were performed at day 47. Systemic expression of mIL-22 was assessed by ELISA.

Results

After confirmation that human RA-SF infected with increasing doses of Ad-mIL-22 expressed high levels of mIL-22 transgene, we demonstrated that the intravenous injection of Ad-mIL-22 in DBA1 mice significantly reduced clinical, radiological and histological scores. By the end of the experiment, the number of arthritic paws was decreased by 70% in the Ad-mIL-22-treated group as compared with controls (P < 0,0001). Ad-mIL-22 resulted in the complete protection as compared with control vector up to 20 days after treatment. Maximal paw widths reached during the course of the disease were, respectively, 1.95 × 0.08 versus 2.76 × 0.60 mm (P = 0.024). Both radiological and histological scores were found to correlate well with clinical observations. Systemic levels of mIL-22 reached 14.2 ± 9.5 ng/ml 4 days after gene transfer, then decreased to 2.4 ± 0.9 ng/ml by day 8 and remained stable until day 21.

Conclusion

Our data support that IL-22 may have antiarthritic properties. The molecular mechanisms responsible for this observation are under investigation.

Authors’ Affiliations

(1)
Unité de Recherches d'Immunopathologie des Maladies Tumorales et Auto-immunes, INSERM U475, Montpellier, France
(2)
Service de Rhumatologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
(3)
Ludwig Institute for Cancer Research, Experimental Medicine Unit, Université Catholique de Louvain, UCL 74.59 Brussels, Belgium
(4)
Service d'Immuno-rhumatologie, CHU Lapeyronie, Montpellier, France

Copyright

© The Author(s) 2004

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