Dear Editor, Hepaticischemia–reperfusion (I/R) injury is a significant medical emergency occurring upon trauma, hepatic surgery, and hemorrhagic shock which leads to acute liver failure, remote organ damage and may limit both liver transplantation and partial hepatectomy surgery. The release of inflammatory mediators is the consequence of ischemia/hypoxia and reperfusion-mediated hepatic injury. Upon severe I/R injury, endogenous danger signals activate the inflammasome complex recruiting caspase-1 cleaving pro-interleukin (IL)-1b into its mature form (Besnard et al., 2012). Upon the IL-1R/Toll-like receptor (TLR) activation and phosphorylation of IkB, NF-kB translocates into the nucleus, and initiates gene expression of IL-23, IL-6, IL-1b, and TGF-b (Llacuna et al., 2009). These mediators together with IL-1b favor the differentiation of IL-17A-producing (Th17) cells expressing IL-23 receptors allowing their expansion by IL-23 produced by innate immune cells (Bettelli et al., 2008). The inflammatory cytokines IL-1 and IL-17A are induced upon organ I/R injury, but their roles in hepatic I/R are elusive. We revisited the role of IL-1 and IL-17A using a model of hepatic I/R injury with 1 h partial ischemia (70%) followed by 6 h reperfusion resulting in hepatic damage.

First, we demonstrate upregulation of hepatic IL-1 and report that hepatic I/R injury, liver inflammation, and neutrophils infiltration are drastically attenuated in IL-1R1 deficient mice (Supplementary Figure S1). We reported before that IL-17A is upregulated in IL-1-dependent lung injury (Gasse et al., 2011), and show here that upon hepatic I/R injury, IL-17A expression is upregulated and IL-1R1 signaling dependent (Supplementary Figure S1F). Moreover, in the liver I/R model, liver damage along with neutrophils influx were