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

Publisher Website
Google Scholar
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)‐α and interferon (IFN)‐γ. 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‐α and IFN‐γ 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.