Pharmacological Inhibition of Type I Interferon Signaling Protects Mice Against Lethal Sepsis

作者：Dejager Lien; Vandevyver Sofie; Ballegeer Marlies; Van Wonterghem Elien; An Ling Ling; Riggs Jeffrey; Kolbeck Roland; Libert Claude^*

来源：Journal of Infectious Diseases, 2014, 209(6): 960-970.

DOI：10.1093/infdis/jit600

• sepsis
• type I interferons
• cecal ligation and puncture
• endotoxemia
• neutrophils

Current research on new therapeutic strategies for sepsis uses different animal models, such as the lipopolysaccharide-induced endotoxemia model and the cecal ligation and puncture (CLP) peritonitis model. By using genetic and pharmacologic inhibition of the type I interferon (IFN) receptor (IFNAR1), we show that type I IFN signaling plays a detrimental role in these sepsis models. Mortality after CLP was reduced even when type I IFN responses were blocked after the onset of sepsis. Our findings reveal that type I IFNs play an important detrimental role during sepsis by negatively regulating neutrophil recruitment. Reduced neutrophil influx likely occurs via the induction of the CXC motif chemokine 1. Moreover, human white blood cells exposed to heat-killed Pseudomonas aeruginosa secrete IFN-beta and stimulate type I IFN signaling. We provide data that support pharmacologic inhibition of type I IFN signaling as a novel therapeutic treatment in severe sepsis.

• 出版日期2014-3-15