Interleukin-6 regulates hepatic transporters during acute-phase response

Biochem Biophys Res Commun. 2004 Sep 10;322(1):232-8. doi: 10.1016/j.bbrc.2004.07.102.


Cholestasis develops during inflammatory conditions characterized by the release of cytokines like interleukin-6 (IL-6), which is the major player in the hepatic acute-phase response. However, the exact contribution of IL-6 to transporter down-regulation is unclear. Therefore, we compared wild-type and IL-6-deficient mice after IL-6-injection and induction of an aseptic (turpentine-injection) or septic (LPS-injection) acute-phase response. Down-regulation of basolateral (Ntcp, Oatp1, and Mrp3) and canalicular (Mrp2, Bsep) transporter mRNA occurred after treatment with IL-6, turpentine, and LPS. In IL-6-deficient mice, turpentine failed to decrease mRNA-levels of basolateral and canalicular transporters, whereas LPS-mediated down-regulation of Ntcp, Mrp3, and Mrp2 was abolished at later time points (24 h). In conclusion, induction of an aseptic and septic acute-phase response leads to the down-regulation of basolateral and canalicular organic anion transporters. IL-6 is required for transporter down-regulation during aseptic inflammation. Furthermore, IL-6 also contributes to transporter regulation during LPS-induced cholestasis at more delayed time points.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction / chemically induced
  • Acute-Phase Reaction / immunology*
  • Acute-Phase Reaction / metabolism*
  • Animals
  • Female
  • Gene Expression Regulation / immunology
  • Interleukin-6 / deficiency
  • Interleukin-6 / immunology*
  • Interleukin-6 / metabolism*
  • Lipopolysaccharides
  • Liver / immunology*
  • Liver / metabolism*
  • Membrane Transport Proteins / immunology
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Turpentine


  • Interleukin-6
  • Lipopolysaccharides
  • Membrane Transport Proteins
  • Turpentine