Interleukin-10 overexpression mediates phenyl-N-tert-butyl nitrone protection from endotoxemia

Shock
Yashige KotakeCharles A Stewart

Abstract

The free radical trapping compound phenyl N-tert-butylnitrone (PBN) provides potent protection against lethal endotoxemia in rodents, but the mechanism of this protection is not well understood. The objective of this study was to show that PBN administration in lipopolysaccharide- (LPS) induced endotoxemia promotes enhanced production of endogenous interleukin 10 (IL-10), and the expressed IL-10 is a causal factor in the protection from endotoxemia. We show the amplified expression of IL-10 in liver and plasma in PBN- (150 mg/kg) plus LPS- (4 mg/kg) treated rats using ribonuclease protection assay (RPA) and ELISA. In situ hybridization was utilized to visualize the overexpression of the IL-10 gene, and ELISA was used to determine plasma IL-10 and TNFalpha levels. Plasma IL-10 showed a 3-fold increase in PBN/LPS- treated rats compared to those treated with LPS alone, and in contrast, TNFalpha level decreased by more than 90%. However, the administration of PBN alone induced no IL-10 production. Immunoneutralization of IL-10 through anti-IL-10 antibody administration to PBN/LPS-treated rats abrogated PBN's suppression of systemic nitric oxide (NO) formation, a surrogate marker for the severity of endotoxemia, indicating that IL-1...Continue Reading

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Citations

Apr 8, 2006·Nephron. Experimental Nephrology·Prasun K DattaElias A Lianos
Dec 26, 2008·World Journal of Gastroenterology : WJG·Tie-Cheng YangAi-Min Ren
Mar 11, 2004·Clinical and Experimental Immunology·E Y BissonnetteM Purcell

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