Inhibition of experimental autoimmune anterior uveitis by adenovirus-mediated transfer of the interleukin-10 gene.
OBJECTIVE
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.
Fang
I-Mo
IM
Department of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
Lin
Chang-Ping
CP
Yang
Chang-Hao
CH
Chiang
Bor-Luen
BL
Yang
Chung-May
CM
Chau
Lee-Young
LY
Chen
Muh-Shy
MS
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000867:Anterior Chamber / Q000276:immunology / Q000473:pathology; D001082:Aqueous Humor / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004195:Disease Models, Animal; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D007958:Leukocyte Count; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014606:Uveitis, Anterior / Q000276:immunology / Q000473:pathology / Q000628:therapy*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10