Adenovirus-mediated viral interleukin-10 gene transfer prevents concanavalin A-induced liver injury

Abstract

Background and aim: 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.

Conclusion: 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.