Sepsis-induced release of interleukin-6 may activate the immediate-early gene program through a hypothalamic-hypophyseal mechanism
Barke, R.A.; Roy, S.; Chapin, R.B.; Charboneau, R.; Brady, P.S.; Brady, L.J.
Surgery 116(2): 141-8; Discussion 148-9
1994
ISSN/ISBN: 0039-6060 PMID: 8047979 Document Number: 424060
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.