Interleukin-39 exacerbates concanavalin A-induced liver injury

Interleukin (IL)-39 is a novel member of IL-12 family and has been reported to play a pro-inflammatory role in lupus-like mice, but its function in concanavalin A (ConA)-induced liver injury is currently unclear.

In this study, we investigated the effects of IL-39 expression in a mouse model of ConA induced-hepatitis. We first showed that delivery of plasmid DNA encoding mouse IL-39 using the hydrodynamic tail vein injection method increased IL-39 mRNA and protein levels in the liver. We then administrated mice with IL-39 plasmid before ConA injection and measured serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, inflammatory infiltration, and hepatocyte necrosis in the liver. Additionally, we further explored the potential mechanism of IL-39 in ConA-induced liver injury by measuring several inflammatory mediators.

We found that ectopic IL-39 expression promoted the ConA-induced increase in serum ALT and AST levels, inflammatory infiltration, and hepatocyte necrosis in the liver. We also observed that IL-39 plasmid administration significantly increased serum and liver interferon-γ, tumor necrosis factor-α, and IL-17A levels, but did not affect serum and liver IL-10 levels in ConA-induced hepatitis.

Our results suggest that IL-39 can exacerbate ConA-induced hepatitis and may be a therapeutic target in inflammatory liver disease.