Inhibition of experimental autoimmune uveoretinitis by systemic and subconjunctival adenovirus-mediated transfer of the viral IL-10 gene

Clin Exp Immunol. 2002 Nov;130(2):212-23. doi: 10.1046/j.1365-2249.2002.01969.x.


Pathological ocular manifestations result from a dysregulation in the balance between proinflammatory type 1 cytokines and regulatory type 2 cytokines. Interleukin-10 (IL-10) is an anti-inflammatory cytokine with potent immunosuppressive effects. We have examined the efficiency of viral IL-10 adenovirus (Ad-vIL-10)-mediated gene transfer on experimental autoimmune uveoretinitis (EAU) induced in mice and rats by purified retinal autoantigens, respectively, interphotoreceptor binding protein (IRBP) and S-antigen (S-Ag). B10-A mice that received a single unilateral injection of Ad-vIL-10 in the retro-orbital sinus venosus performed 1 day before immunization with IRBP in the footpads showed high levels of circulating vIL-10 in their sera and a significant reduction in pathological ocular manifestations. Lower levels of IFN-gamma and IL-2 were found in cellular supernatants from IRBP-stimulated splenic cells in these treated mice. The local effect on ocular disease of vIL-10 was neutralized completely by injection of a monoclonal anti-vIL-10 antibody, demonstrating the specificity of the treatment. To determine whether the transfer of the vIL-10 gene within the periocular tissues of the eye could prevent acute EAU, a subconjunctival injection of Ad-vIL-10 was performed in Lewis rats simultaneously with S-antigen in the footpads. This injection determined in situ vIL-10 expression with very low circulating vIL-10 and led to a significant reduction of EAU without affecting the systemic immune response. The present results suggest that Ad-mediated gene transfer resulting in systemic and local expression of vIL-10 provide a promising approach for the treatment of uveitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / prevention & control*
  • Cells, Cultured
  • Conjunctiva
  • Eye / chemistry
  • Eye / metabolism
  • Eye Proteins*
  • Female
  • Genes, Viral
  • Genetic Therapy
  • Genetic Vectors / administration & dosage
  • Green Fluorescent Proteins
  • Immunoglobulin G / blood
  • Injections
  • Injections, Intravenous
  • Interleukin-10 / blood
  • Interleukin-10 / genetics*
  • Luminescent Proteins / analysis
  • Luminescent Proteins / genetics
  • Male
  • Mice
  • Rats
  • Rats, Inbred Lew
  • Retinitis / immunology
  • Retinitis / pathology
  • Retinitis / prevention & control*
  • Retinol-Binding Proteins / immunology
  • Th1 Cells / immunology
  • Uveitis / immunology
  • Uveitis / pathology
  • Uveitis / prevention & control*
  • beta-Galactosidase / analysis
  • beta-Galactosidase / genetics


  • Eye Proteins
  • Immunoglobulin G
  • Luminescent Proteins
  • Retinol-Binding Proteins
  • interstitial retinol-binding protein
  • Interleukin-10
  • Green Fluorescent Proteins
  • beta-Galactosidase