Endogenous Interleukin 18 Suppresses Liver Regeneration After Hepatectomy in Mice

The comprehensive role of interleukin (IL) 18 during liver regeneration is barely studied. Our aim is to evaluate the role of IL18 in liver regeneration after partial hepatectomy (PH) in mice. The expression profile of IL18 in the liver and the gut after 70% PH was measured. Liver samples after 70% and 85% PH from IL18 knockout (IL18(-/-)) mice and wild type (WT) mice were collected for comparison of liver regeneration. The effect of recombinant IL18 on liver regeneration was tested in IL18(-/-) mice, and the utility of IL18 binding protein (BP) was also evaluated following 70% PH in WT mice. Expression levels of IL18 in the liver and the gut elevated after 70% PH. The liver weight/body weight ratios (LBWRs) after PH were significantly higher in IL18(-/-) mice than those in WT mice. Recombinant IL18 injection significantly decreased LBWR at 7 days after 70% PH in IL18(-/-) mice. The expression of cyclin D1, EdU labeling index, and Ki-67 proliferation index were much higher in IL18(-/-) mice than those in WT mice after 70% PH. The expression level of glypican 3 (GPC3) in WT mice significantly elevated during liver regeneration. In contrast, the expression level of GPC3 in IL18(-/-) mice remained roughly unchanged during liver regeneration. IL18BP injection significantly increased the LBWR at 7 days after 70% PH in WT mice. In conclusion, endogenous IL18 inhibited liver regeneration after PH in mice, possibly through up-regulating GPC3. IL18BP may be an effective agent to promote liver regeneration after PH.