Hepatic inflammasome activation as origin of Interleukin-1α and Interleukin-1β in liver cirrhosis
Michael Praktiknjo, Robert Schierwagen, Sofia Monteiro, Cristina Ortiz, Frank Erhard Uschner, Christian Jansen, Joan Clària, Jonel Trebicka
Abstract
We appreciate the interest of Stengel et al 1 in our recent multicenter study published in Gu t.1 2 The group suggests that peripheral blood mononuclear cells (PBMC) are a source of interleukin (IL)-1β in acute decompensation (AD) independent of the canonical inflammasome activation pathway.1 While we acknowledge this meticulous work performed, we still think that the source of IL-1 and, therefore, the site of inflammasome activation is rather the diseased liver than circulating PBMC. Especially since in our work, we found these pathways persistently increased even in compensated, recompensated and decompensated cirrhosis. In order to prove the origin of IL-1α and IL-1β, we assessed gene expression in PBMC and liver from our animal model of compensated and recompensated (after recovery from AD) cirrhosis. In this model, bile duct ligation in rats was used to induce liver cirrhosis and lipopolysaccharide to induce AD as described previously.2 Gene expression of both IL-1α and IL-1β is significantly higher in liver tissue compared with PBMC in recompensated cirrhosis. In compensated cirrhosis, gene expression of IL-1α, but not IL-1β, is significantly increased in liver tissue compared with PBMC (figure 1A,B). Figure 1 (A) Gene expression of interleukin (IL)-1α and (B) IL-1β in liver tissue and peripheral …