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  • Title: Enhancement of endotoxin-induced interleukin-10 production by SR 31747A, a sigma ligand.
    Author: Bourrie B, Bouaboula M, Benoit JM, Derocq JM, Esclangon M, Le Fur G, Casellas P.
    Journal: Eur J Immunol; 1995 Oct; 25(10):2882-7. PubMed ID: 7589087.
    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.
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