title: Sepsis-induced release of interleukin-6 may activate the immediate-early gene program through a hypothalamic-hypophyseal mechanism.
abstract: BACKGROUND
  The immediate-early gene c-fos has been implicated in transcriptional regulation after sepsis. We test the hypothesis that sepsis-induced central nervous system release of interleukin (IL)-6 regulates hepatic c-fos gene expression.
  
  
  METHODS
  Using a stereotaxically placed intracerebral-ventricular (ICV) catheter in rats with and without hypophysectomy, we measured hepatic c-fos protein accumulation after treatment with either IL-6 or vehicle control. Using a rat cecal ligation and puncture (CLP) model, we studied the following groups: (1) sham-CLP, (2) CLP, (3) hypophysectomized sham-CLP, and (4) hypophysectomized CLP and measured hepatic c-fos mRNA.
  
  
  RESULTS
  ICV IL-6 treatment increased hepatic c-fos protein in the IL-6-treated group compared with the vehicle-treated group, and hypophysectomy inhibited the ICV IL-6-mediated increase in c-fos protein. After peritoneal sepsis, CLP increased hepatic c-fos messenger RNA compared to either the sham-CLP or the hypophysectomized sham-CLP group, and hypophysectomy before CLP inhibited hepatic c-fos mRNA compared with the CLP group.
  
  
  CONCLUSIONS
  ICV IL-6 results in an increase in hepatic fos protein that is mediated through a hypothalamic-hypophyseal mechanism. Peritoneal sepsis results in an increase in hepatic c-fos gene expression that may be, in part, mediated by central nervous system release of IL-6 through a hypothalamic-hypophyseal mechanism.
authors.affiliation: Department of Surgery, University of Minnesota, Minneapolis.
authors.forename: R A
authors.initials: RA
authors.lastname: Barke
authors.forename: S
authors.initials: S
authors.lastname: Roy
authors.forename: R B
authors.initials: RB
authors.lastname: Chapin
authors.forename: R
authors.initials: R
authors.lastname: Charboneau
authors.forename: P S
authors.initials: PS
authors.lastname: Brady
authors.forename: L J
authors.initials: LJ
authors.lastname: Brady
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000378:metabolism*; D001483:Base Sequence; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D016762:Genes, fos; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015850:Interleukin-6; D012333:RNA, Messenger