Inhibition of experimental autoimmune anterior uveitis by adenovirus-mediated transfer of the interleukin-10 gene

J Ocul Pharmacol Ther. 2005 Dec;21(6):420-8. doi: 10.1089/jop.2005.21.420.

Abstract

Aims: The aim of this study was to investigate the efficiency of adenoviral-mediated transfer of the interleukin (IL)-10 gene for inhibition of experimental autoimmune anterior uveitis, a rat model of human acute anterior uveitis. Uveitis was induced in the Lewis rat by simultaneous injection of melanin-associated antigen intraperitoneally (i.p.) and into the left footpad. The animals were treated by systemic administration of adenoviral construct expressing IL-10 (Ad-IL-10) or Ad-Mock carrying no cytokine transgene.

Results: A significant reduction in ocular inflammation was noted for rats that received one or two divided i.p. administrations of Ad-IL-10 (one 10 x 10(9) and two 5 x 10(9) particles of adenoviral construct, respectively), as judged by reduced clinical scores and decreased leukocyte infiltration in the anterior chamber and confirmed by histological examinations, relative to control animals. Systemic Ad-IL-10, treatment also revealed a higher serum level of IL-10, compared to the controls.

Conclusions: The results suggest that systemic adenovirus-mediated IL-10 gene therapy has an anti-inflammatory effect on immune-mediated ocular inflammation and that this approach may be promising for the treatment of acute anterior uveitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae* / genetics
  • Animals
  • Anterior Chamber / immunology
  • Anterior Chamber / pathology
  • Aqueous Humor / immunology
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / therapy*
  • Chemotaxis, Leukocyte / immunology
  • Disease Models, Animal
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / blood
  • Interleukin-10 / genetics*
  • Leukocyte Count
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Polymerase Chain Reaction
  • Rats
  • Rats, Inbred Lew
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Uveitis, Anterior / immunology
  • Uveitis, Anterior / pathology
  • Uveitis, Anterior / therapy*

Substances

  • Tumor Necrosis Factor-alpha
  • Interleukin-10