SEPSIS-INDUCED RELEASE OF INTERLEUKIN-6 MAY ACTIVATE THE IMMEDIATE-EARLY GENE PROGRAM THROUGH A HYPOTHALAMIC-HYPOPHYSEAL MECHANISM

Background. The immediate-early gene c-fos has been implicated in tran scriptional regulation after sepsis. We test the hypothesis that sepsi s-induced central nervous system release of interleukin (IL)-6 regulat es hepatic c-fos gene expression. Methods. Using a stereotaxically pla ced intracerebral-ventricular (ICV) catheter in rats with and without hypophysectomy, we measured hepatic c-fos protein accumulation after t reatment with either IL-6 or vehicle control. Using a rat cecal ligati on and puncture (CLP) model, we studied the following groups: (1) sham -CLP, (2) CLP, (3) hypophysectomized sham-CLP, and (4) hypophysectomiz ed CLP and measured hepatic c-fos mRNA. Results. ICV IL-6 treatment in creased hepatic c-fos protein in the IL-6-treated group compared with the vehicle-treated group, and hypophysectomy inhibited the ICV IL-6-m ediated increase in c-fos protein. After peritoneal sepsis, CLP increa sed hepatic c-Sos messenger RNA compared to CLP inhibited hepatic c-fo s mRNA compared with the CLP group. Conclusions. ICV IL-6 results in a n increase in hepatic Jos protein that is mediated through a hypothala mic-hypophyseal mechanism. Peritoneal sepsis results in an increase in hepatic c-fos gene expression that may be, in part, mediated by centr al nervous system release of IL-6 through a hypothalamic-hypophyseal m echanism.