Interleukin-10 expression and function in experimental murine liver inflammation and fibrosis

Hepatology. 1998 Dec;28(6):1597-606. doi: 10.1002/hep.510280620.


Kupffer cells (KC) play a central role in the initiation and perpetuation of hepatic inflammation, which, if uncontrolled, can result in tissue damage, fibrosis, and cirrhosis. Interleukin-10 (IL-10) can inhibit a range of macrophage functions. We hypothesized that the transcription, synthesis, and release of IL-10 may influence the development of liver injury. Rat KC were activated in vitro with lipopolysaccharide (LPS), and expression of IL-10 mRNA compared with IL-13 and IL-1beta by reverse-transcription polymerase chain reaction (RT-PCR). The effects of pretreatment with recombinant IL-10 (rIL-10) on KC phagocytosis, production of superoxide (SO), and tumor necrosis factor (TNF-) were examined by fluorescent activated cell sorter (FACS), reduction of ferricytochrome C, and bioassay, respectively. Rats were administered intraperitoneal carbon tetrachloride (CCl4), and expression of IL-10 mRNA and protein in vivo compared with IL-13 and IL-1beta by RT-PCR and immunoblotting. Results were correlated with histological inflammatory changes. Finally, IL-10 gene-deleted (IL-10-/-) mice and wild-type (WT) controls were administered intraperitoneal CCl4 biweekly for up to 70 days, and the development of inflammation and fibrosis compared by scoring histological changes. IL-10 mRNA was up-regulated early, both in KC in vitro and in whole liver in vivo, concurrent with that of IL-1beta. IL-10 was able to inhibit KC production of both SO and TNF- in vitro, and this was achieved more effectively than IL-4 or IL-13; no such effects were seen on KC phagocytosis. After 70 days of treatment with CCl4, IL-10-/- mice showed significantly more severe fibrosis and exhibited higher hepatic TNF- levels than WT controls. These results suggest that IL-10 synthesized during the course of liver inflammation and fibrosis may modulate KC actions, and influence subsequent progression of fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbon Tetrachloride
  • Cells, Cultured
  • Cytokines / pharmacology
  • Female
  • Hepatitis, Animal / metabolism
  • Hepatitis, Animal / pathology
  • Hepatitis, Animal / physiopathology*
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics
  • Interleukin-10 / pharmacology
  • Interleukin-10 / physiology*
  • Kupffer Cells / drug effects
  • Kupffer Cells / physiology
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis, Experimental / chemically induced
  • Liver Cirrhosis, Experimental / metabolism
  • Liver Cirrhosis, Experimental / pathology
  • Liver Cirrhosis, Experimental / physiopathology*
  • Male
  • Mice
  • Phagocytosis / physiology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Carbon Tetrachloride