Adenovirus-mediated viral interleukin-10 gene transfer prevents concanavalin A-induced liver injury.
OBJECTIVE
Liver injury is closely associated with immune inflammation. Lacking immunostimulatory functions, viral interleukin-10 (vIL-10), a cellular IL-10 homologue, has been an attractive molecule for immunomodulatory therapy. We aimed to reveal a protective effect of the gene transfer of an adenoviral vector encoding vIL-10 on liver injury induced by concanavalin A.


METHODS
C57BL/6J mice were intravenously injected with adenoviral vector encoding vIL-10 before concanavalin A challenge. Liver injury was assessed. Interferon-γ and interleukin-4 levels were measured by ELISA. The activation of splenic and hepatic immune cells was analysed using an MTT assay.


RESULTS
Adenoviral vector encoding vIL-10 pretreatment significantly decreased concanavalin A-mediated elevations in serum alanine aminotransaminase and aspartate aminotransaminase activity, and necrotic area in liver tissues. The protective effect of adenoviral vector encoding vIL-10 was attributed to its inhibition of T cell activation, and production of interferon-γ and interleukin-4 by the immune cells. Recombinant mouse IL-10, a high homologous cytokine to vIL-10, effectively downregulated interferon-γ and interleukin-4 release by hepatic mononuclear cells.


CONCLUSIONS
Adenovirus vector-mediated vIL-10 gene transfer can prevent concanavalin A-induced hepatic injury, minimise pro-inflammatory cytokine release, and inhibit the activation of T lymphocytes.
Institute of Inflammation and Immune Diseases, Shantou University Medical College, Shantou, Guangdong, China.
Yan-Chun
YC
Zhou
Sui
S
Chen
Jun-Jun
JJ
Cao
Shao-Ying
SY
Chen
Yan-Fei
YF
Xie
Qing-Xia
QX
Niu
D000256:Adenoviridae / Q000235:genetics*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003208:Concanavalin A / Q000008:administration & dosage / Q000009:adverse effects*; D015536:Down-Regulation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics*; D015847:Interleukin-4 / Q000378:metabolism; D008099:Liver / Q000166:cytology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000008:administration & dosage / Q000009:adverse effects*; D009000:Monocytes / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D008934:Mitogens; D003208:Concanavalin A; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase