In Vivo Expression of Interleukin-37 Reduces Local and Systemic Inflammation in Concanavalin A-Induced Hepatitis

Abstract

We recently reported that after LPS stimulation, IL-37 translocates to the nucleus and reduces the expression of proinflammatory cytokines. The aim of this study was to investigate whether transiently expressed IL-37 in mice reduces inflammation in concanavalin A (ConA)-induced hepatitis and LPS-induced sepsis. Transgene IL-37 expression was detected in the liver lysate of mice injected with IL-37 plasmid-DNA after hydrodynamic tail vein injection. All mice developed severe acute hepatitis after ConA injection. No difference in the histological score and serum ALT was observed between the two groups that might be explained by patchy expression of IL-37 protein in the liver. However, 2 hrs after ConA injection, serum levels for IL-1α, IL-6, IL-5, and IL-9 were significantly reduced in IL-37-expressing mice as seen for the LPS model. In conclusion, in vivo expression of human IL-37 in mice reduces local and systemic inflammation in ConA-induced hepatitis and LPS challenge.