Activation of NF-kappa B after chronic ethanol intake and haemorrhagic shock/resuscitation in mice

作者：Maraslioglu M^*; Weber R; Korff S; Blattner C; Nauck C; Henrich D; Jobin C; Marzi I; Lehnert M

来源：British Journal of Pharmacology, 2013, 170(3): 506-518.

DOI：10.1111/bph.12224

• chronic ethanol
• haemorrhage
• resuscitation
• NF-kappa B
• liver injury
• inflammation

Background and PurposeChronic ethanol abuse and haemorrhagic shock are major causes of global mortality and, separately, induce profound hepato- and immune-toxic effects via activation of NF-B. Here, we assessed the effects of chronic ethanol intake upon the pathophysiological derangements after haemorrhagic shock with subsequent resuscitation (H/R), with particular attention to the contribution of NF-B. %26lt;br%26gt;Experimental ApproachTransgenic NF-B-EGFP mice, expressing the enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-B cis-elements were fed a Lieber-DeCarli diet containing ethanol (EtOH-diet) or an isocaloric control diet for 4 weeks and were then pairwise subjected to H/R. Liver tissues and peripheral blood were sampled at 2 or 24h after H/R. Cytokines in blood and tissue and leukocyte activation (as CD11b expression) were measured, along with EGFP as a marker of NF-B activation. %26lt;br%26gt;Key ResultsThe EtOH-diet increased mortality at 24h after H/R and elevated liver injury, associated with an up-regulation of NF-B-dependent genes and IL-6 release; it also increased production of NF-B-driven intercellular adhesion molecule 1 (ICAM-1) and EGFP in liver tissue. At 2h after the H/R procedure in ethanol-fed mice we observed the highest proportion of NF-B activated non-parenchymal cells and an NF-B-dependent increase in polymorphonuclear leukocyte CD11b expression. %26lt;br%26gt;Conclusions and ImplicationsThe EtOH-diet exacerbated liver injury after H/R, accompanying an overwhelming hepatic and systemic immune response. Our findings contribute to evidence implicating NF-B as a key player in the orchestration of the immune response in haemorrhagic shock patients with a history of chronic ethanol abuse.

• 出版日期2013-10