Interleukin-10 controls interferon-gamma and tumor necrosis factor production during experimental endotoxemia

Eur J Immunol. 1994 May;24(5):1167-71. doi: 10.1002/eji.1830240524.


Interleukin-10 (IL-10) is a potent inhibitor of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production and has been shown to protect mice from endotoxin shock. As IFN-gamma is another important mediator of LPS toxicity, we studied the effects of IL-10 on LPS-induced IFN-gamma synthesis in vitro and in vivo. First, we found that the addition of recombinant human IL-10 (rhIL-10) (10 U/ml) to human whole blood markedly suppressed LPS-induced IFN-gamma release while neutralization of endogenously synthesized IL-10 resulted in increased IFN-gamma levels. The ability of rIL-10 to inhibit LPS-induced IFN-gamma synthesis was also observed in vivo in mice. Indeed, administration of 1000 U recombinant mouse IL-10 (rmIL-10) 30 min before and 3 h after challenge of BALB/c mice with 100 micrograms LPS resulted in a threefold decrease in peak IFN-gamma serum levels. We then examined the production and the role of IL-10 during murine endotoxemia. We found that LPS injection causes the rapid release of IL-10, peak IL-10 serum levels being observed 90 min after LPS challenge. Neutralization of endogenously produced IL-10 by administration of 2 mg JES5-2A5 anti-IL-10 monoclonal antibody (mAb) 2 h before LPS challenge resulted in a marked increase in both TNF and IFN-gamma serum levels while irrelevant isotype-matched mAb had no effect. The enhanced production of inflammatory cytokines in anti-IL-10 mAb-treated mice was associated with a 60% lethality after injection of 500 micrograms LPS, while all mice pretreated with control mAb survived. We conclude that the rapid release of IL-10 during endotoxemia is a natural antiinflammatory response controlling cytokine production and LPS toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Cytokines / biosynthesis*
  • Endotoxins / blood*
  • Humans
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / pharmacology
  • Interleukin-10 / physiology*
  • Lipopolysaccharides
  • Mice
  • Mice, Inbred BALB C
  • Recombinant Proteins / pharmacology
  • Toxemia / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Antibodies, Monoclonal
  • Cytokines
  • Endotoxins
  • Lipopolysaccharides
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interferon-gamma