Open AccessInhibition of experimental autoimmune uveoretinitis by systemic and subconjunctival adenovirus‐mediated transfer of the viral IL‐10 gene
Author(s) -
DE KOZAK Y.,
THILLAYEGOLDENBERG B.,
NAUD M.C.,
DA COSTA A. VIANA,
AURIAULT C.,
VERWAERDE C.
Publication year - 2002
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.2002.01969.x
Subject(s) - proinflammatory cytokine , immunology , antigen , cytokine , autoimmune disease , immune system , antibody , medicine , inflammation
Summary 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‐ γ 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.