Production and role of interleukin-10 in concanavalin A-induced hepatitis in mice

Hepatology. 1997 Jun;25(6):1382-9. doi: 10.1002/hep.510250614.


Experimental T-cell-mediated hepatitis induced by concanavalin A (Con A) involves the production of proinflammatory cytokines. Because interleukin (IL)-10 is a potent anti-inflammatory cytokine derived from macrophages and T cells and is produced within the liver, we investigated the role of IL-10 in modulating the hepatotoxicity and the secretion of cytokines following in vivo injection of Con A. IL-10 is produced early in the serum after Con A challenge. Neutralization of endogenous IL-10 by monoclonal antibodies (mAbs) increases the secretion of tumor necrosis factor alpha (TNF-alpha) (+111%), interferon gamma (IFN-gamma) (+92%), and IL-12 (+730%) 8 hours after Con A injection, and increases the hepatotoxicity, assessed by serum alanine transaminase (ALT) (+174%) measurement and by histology, 24 hours after induction of hepatitis. Conversely, preadministration of recombinant IL-10 reduces the production of these proinflammatory cytokines (-47%, -80%, and -47% for TNF-alpha, IL-12, and IFN-gamma, respectively), and decreases neutrophil infiltration and ALT serum concentration (-74%) 8 hours after Con A challenge. We conclude that IL-10, either endogenously produced or exogenously added, has a hepatoprotective role in Con A-induced hepatitis, through its suppressive property on proinflammatory cytokine production, and that it might be of therapeutic relevance in human liver diseases involving activated T cells.

MeSH terms

  • Animals
  • Chemical and Drug Induced Liver Injury / physiopathology*
  • Concanavalin A*
  • Interferon-gamma / antagonists & inhibitors
  • Interferon-gamma / metabolism
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / pharmacology
  • Interleukin-10 / physiology*
  • Interleukin-12 / antagonists & inhibitors
  • Interleukin-12 / metabolism
  • Liver / drug effects
  • Liver / pathology
  • Mice
  • Mice, Inbred C3H
  • Necrosis
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism


  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Concanavalin A
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma