IL-33 induces nuocytes and modulates liver injury in viral hepatitis (P6112)

Abstract

Abstract Our aim was to investigate the role of IL-33, the damage-associated molecular pattern (DAMP) molecule, in acute viral hepatitis. C57BL/6 mice were i.v. infected with a recombinant adenovirus. IL-33 and its receptor ST2 expression increased steadily in the liver in the first week of the infection. Treatment of exogenous IL-33 resulted in a great decrease in the serum alanine aminotransferase (ALT) levels and the number of Councilman bodies. Attenuated liver injury by IL-33 correlated with an increase in T regulatory (Treg) cells but with a decrease in macrophages, dendritic cells and NK cells in the liver. IL-33 enhanced both type 1 (IL-2, IFN-γ) and type 2 (IL-5, IL-13) immune responses in infected mice. However, IL-33 inhibited TNF-α in hepatic T cells and macrophages, and significantly reduced TNF-α levels in the liver. In addition to direct effects of IL-33, we found that IL-33 strongly induced nuocytes in the liver and spleen of infected mice. When co-cultured with nuocytes, hepatic T cells and macrophages expressed lower levels of TNF-α. In addition, the adoptive transfer of nuocytes led to lower serum ALT levels in the Ad-infected recipient mice. In conclusion, this study reveals that IL-33 acts as a potent immune stimulator and a hepatoprotective cytokine in acute viral hepatitis. Its direct immunoregulatory functions and ability to induce nuocytes further suggest to us that it may be a potentially promising therapeutic candidate for the management of viral hepatitis.