Volume 3 Supplement 1

Innovative Rheumatology: Gene and Cell Therapies of Arthritis and Related Autoimmune Disorders. Second International Meeting

Open Access

Inhibition of collagen-induced arthritis in mice by inducible AAV-mediated transfer of viral IL-10 gene

  • F Apparailly1,
  • V Millet1,
  • C Jacquet1,
  • J Sany1,
  • C Noël1 and
  • C Jorgensen1
Arthritis Research & Therapy20013(Suppl 1):P24

https://doi.org/10.1186/ar350

Received: 6 April 2001

Published: 25 April 2001

Objective

The purpose of this study is to assess the therapeutic efficiency of vIL-10 gene transfer mediated by a tetracycline-inducible AAV vector in mice model of arthritis.

Method

The AAV-tetON-vIL10 vector (1.5 × 109 pi) was injected intramuscularly 3 weeks before immunization with bovine type II collagen. DBA1 mice with collagen-induced arthritis then received dox diet (200 mg/kg) from days 21–42 of immunization. Severity of arthritis was determined by measuring paw swelling, evaluating X-ray and histological paw features. Expression of vIL-10 was measured by RT-PCR and ELISA in injected muscle.

Results

The incidence and severity of arthritis was significantly reduced at macroscopic, radiologic and histologic levels in the group of animals treated with AAV-TetON-vIL10 vector plus doxycycline, compared with vector alone or control groups (AAV-GFP + doxycycline and doxycycline alone). Only 30% of mice developed arthritis against 89% in controls. Mice from the control groups showed earlier onset of arthritis, with clinical signs of the disease starting on day 32.63 ± 4.07, compared with 36.67 ± 3.51 in the AAV-TetON-vIL10 injected group treated with doxycycline (P = 0.033). The benefit was not only observed at the inflammatory level, but also on cartilage and bone erosion (P < 0.01). Gene transfer led to detectable levels of vIL-10 transcript and protein in the AAV-tetON-vIL10 injected muscles, inducible by doxycycline. A basal transcription of vIL-10 was observed, significantly induced by doxycycline (× 2.7, P = 0.0094), leading to a higher secretion of vIL-10 protein (284.4 ± 358.2 versus 181.9 ± 130.2 pg/mg protein, NS). The biodistribution of the vector genome beyond the site of injection was determined by RT-PCR, vIL-10 transcript was found in five out of 29 spleens.

Conclusion

These data support AAV-tetON-vIL10 as a valuable approach for anti-inflammatory gene therapy in RA.

Authors’ Affiliations

(1)
INSERM U475, CHU Lapeyronie

Copyright

© BioMed Central Ltd 2001

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