Rapid and simultaneous activation of Stat3 and production of interleukin 6 in resuscitated hemorrhagic shock.

The inflammatory response of the liver to hemorrhagic shock includes the production of acute phase proteins and a variety of mediators, such as the cytokine interleukin (IL)-6. The transcription of acute phase protein genes in hepatocytes has been shown to be activated by Stat3, one of six distinct signal transducers and activators of transcription (STAT) proteins. IL-6 signals through activation of Stat3. In this study, we examined whether or not Stat3 was activated and IL-6 mRNA produced in the liver of rats subjected to hemorrhagic shock and whether or not both phases of shock, the ischemic and the resuscitation phases, were required. We report here that Stat3 activation and increased IL-6 expression required resuscitation and displayed identical kinetics following resuscitation, suggesting that liver production of IL-6 was responsible for liver Stat3 activation in hemorrhagic shock.