Enhancement of endotoxin-induced interleukin-10 production by SR 31747A, a sigma ligand

Eur J Immunol. 1995 Oct;25(10):2882-7. doi: 10.1002/eji.1830251026.

Abstract

SR 31747A is a new sigma ligand eliciting immunosuppressive and anti-inflammatory properties. Here, we show that SR 31747A greatly enhances lipopolysaccharide (LPS)-induced systemic release of interleukin (IL)-10, while it inhibits the secretion of tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. In line with this finding, we also show by using quantitative reverse transcription-polymerase chain reaction analysis that SR 31747A increased LPS-induced IL-10 mRNA accumulation in spleen cells, whereas the level of both TNF-alpha and IFN-gamma mRNA was dramatically decreased. The enhancement of IL-10 production by SR 31747A treatment was also apparent in nude and severe-combined immunodeficient mice treated with LPS, clearly indicating that T and B cells were not involved. Finally, SR 31747A conferred protection against the lethal effect of LPS. The finding that SR 31747A strongly stimulates the synthesis of the natural anti-inflammatory cytokine IL-10, a property not observed with dexamethasone, provides new insights for the clinical use of this original compound, particularly in chronic inflammatory diseases where IL-10 is believed to be a pivotal regulatory component.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Base Sequence
  • Cyclohexanes / pharmacology*
  • Cyclosporine / pharmacology
  • DNA, Complementary / genetics
  • Dexamethasone / pharmacology
  • Female
  • Galactosamine / toxicity
  • Immunosuppressive Agents / pharmacology*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Interleukin-10 / biosynthesis*
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Lipopolysaccharides / pharmacology
  • Lipopolysaccharides / toxicity
  • Lymphocyte Subsets / drug effects
  • Lymphocyte Subsets / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mice, SCID
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptors, sigma / agonists*
  • Shock, Septic / prevention & control
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclohexanes
  • DNA, Complementary
  • Immunosuppressive Agents
  • Lipopolysaccharides
  • RNA, Messenger
  • Receptors, sigma
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Galactosamine
  • Dexamethasone
  • Interferon-gamma
  • Cyclosporine
  • SR 31747