Volume 6 Supplement 1

24th European Workshop for Rheumatology Research

Open Access

IL-22 gene transfer in collagen-induced arthritis

  • F Apparailly1,
  • J Dudler2,
  • J-C Renauld3,
  • P Plence1,
  • L Dumoutier3,
  • F Djouad1,
  • D Noel1,
  • AK So2,
  • J Sany1, 2, 3, 4 and
  • C Jorgensen1, 2, 3, 4
Arthritis Res Ther20046(Suppl 1):81

https://doi.org/10.1186/ar1123

Received: 16 January 2004

Published: 24 February 2004

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
(2)
Service de Rhumatologie, Centre Hospitalier Universitaire Vaudois
(3)
Ludwig Institute for Cancer Research, Experimental Medicine Unit, Université Catholique de Louvain
(4)
Service d'Immuno-rhumatologie, CHU Lapeyronie

Copyright

© The Author(s) 2004

Advertisement