Background: Hepatic ischemia and reperfusion (I/R) is common in liver surgery and transplantation and compromises postoperative liver function. Hepatic I/R is characterized by sterile inflammation that contrib-utes to hepatocellular necrosis. Many immune cells and cytokines have been implicated in hepatic I/R. However, the role and relevance of IL-23 and IL-17 remains controversial in literature.
Aim: To determine whether the IL-23/IL-17 signaling axis is activated in hepatic I/R using a triple-level experimental approach (in vitro, in vivo, and clinical).
Methods: IL-23 and IL-17 were assayed by ELISA in the supernatant of cultured murine (RAW 264.7) macrophages that were activated by supernatant fractions of necrotic cultured mouse (AML12) hepatocytes. Similarly, levels of these cytokines were determined in plasma samples and liver tissue of mice (N = 85) subjected to 70% partial liver I/R. Finally, IL-23 and IL-17 were assayed in plasma samples obtained from a controlled cohort of liver resection patients who were either subjected to I/R (N = 27) or not (N = 13).
Results: Activated macrophages did not produce IL-23 in response to necrotic cell-rich supernatant. IL-23 and IL-17 were not elevated in mice subjected hepatic I/R and were not elevated in serum from patients subjected to I/R during liver resection. Conclusions: IL-23 and IL-17 are not involved in hepatic I/R injury in mouse and man.
Relevance for patients: If IL-23 and IL-17 were to mediate hepatocellular injury following I/R, these cyto-kines would constitute potential therapeutic targets. Since this study has revealed that IL-23 and IL-17 do not play a role in hepatic I/R, other pathways and therapeutic targets should be considered when developing modalities aimed at reducing hepatic I/R injury.
1 Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
2 Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Department of Experimental Surgery, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
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Department of Membrane Biochemistry and Biophysics, Utrecht University, Utrecht, the Netherlands