The contralateral effect conferred by intra-articular adenovirus-mediated gene transfer of viral IL-10 is specific to the immunizing antigen

E. R. Lechman, A. Keravala, J. Nash, S. H. Kim, Z. Mi, P. D. Robbins

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

We have demonstrated previously that local, adenoviral-mediated gene transfer of vIL-10 to a single joint of rabbits and mice with experimental arthritis can suppress disease in both the treated and untreated contralateral joints. These therapeutic effects observed in distant untreated joints following local intra-articular gene delivery have been termed the 'contralateral effect'. To begin to understand the underlying immunologic mechanism that confers this effect, a dual-antigen model of antigen-induced arthritis (AIA) in rabbit knee joints was utilized. Rabbits were immunized against two antigens, ovalbumin and keyhole limpet hemocyanin, and AIA generated by intra-articular injection of each antigen into contralateral knees. Intra-articular adenovirus-mediated gene transfer of vIL-10 significantly reduced intra-articular leukocytosis and cartilage matrix degradation, while preserving near normal levels of cartilage matrix synthesis within treated joints. However, no antiarthritic effect was conferred in the contralateral control joints that received only a marker gene, in contrast to the results seen in a single-antigen AIA model. These results suggest that the distant antiarthritic effects associated with local gene delivery to joints are antigen-specific, and not due to vIL-10-induced generalized immunosuppression of the animal.

Original languageEnglish (US)
Pages (from-to)2029-2035
Number of pages7
JournalGene therapy
Volume10
Issue number24
DOIs
StatePublished - Nov 2003

Bibliographical note

Funding Information:
We would like to thank Steve Ghivizzani, Tom Oligino and Chris Evans for helpful discussions. We would especially like to thank Jeff Mai for his technical expertise. The work was supported in part by Grants AR-6-2225 and DK44935 from the National Institutes of Health.

Keywords

  • Antigen-induced arthritis
  • Autoimmunity
  • Contralateral effect
  • Distant therapeutic effects
  • Rheumatoid arthritis

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