PMID- 8047979 OWN - NLM STAT- MEDLINE DCOM- 19940830 LR - 20181130 IS - 0039-6060 (Print) IS - 0039-6060 (Linking) VI - 116 IP - 2 DP - 1994 Aug TI - Sepsis-induced release of interleukin-6 may activate the immediate-early gene program through a hypothalamic-hypophyseal mechanism. PG - 141-8; discussion 148-9 AB - 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. FAU - Barke, R A AU - Barke RA AD - Department of Surgery, University of Minnesota, Minneapolis. FAU - Roy, S AU - Roy S FAU - Chapin, R B AU - Chapin RB FAU - Charboneau, R AU - Charboneau R FAU - Brady, P S AU - Brady PS FAU - Brady, L J AU - Brady LJ LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Surgery JT - Surgery JID - 0417347 RN - 0 (Interleukin-6) RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Bacterial Infections/*metabolism MH - Base Sequence MH - *Gene Expression Regulation MH - *Genes, Immediate-Early MH - *Genes, fos MH - Hypothalamo-Hypophyseal System/*physiology MH - Interleukin-6/*metabolism MH - Male MH - Molecular Sequence Data MH - RNA, Messenger/analysis MH - Rats MH - Rats, Sprague-Dawley EDAT- 1994/08/01 00:00 MHDA- 1994/08/01 00:01 CRDT- 1994/08/01 00:00 PHST- 1994/08/01 00:00 [pubmed] PHST- 1994/08/01 00:01 [medline] PHST- 1994/08/01 00:00 [entrez] PST - ppublish SO - Surgery. 1994 Aug;116(2):141-8; discussion 148-9.