Weijer Sebastiaan, Sewnath Miguel E, de Vos Alex F, Florquin Sandrine, van der Sluis Koen, Gouma Dirk J, Takeda Kiyoshi, Akira Shizuo, van der Poll Tom
Laboratory of Experimental Internal Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, Room L0185, 1105 AZ Amsterdam, The Netherlands.
Infect Immun. 2003 Oct;71(10):5488-97. doi: 10.1128/IAI.71.10.5488-5497.2003.
To determine the role of endogenous interleukin-18 (IL-18) during peritonitis, IL-18 gene-deficient (IL-18 KO) mice and wild-type mice were intraperitoneally (i.p.) infected with Escherichia coli, the most common causative agent found in septic peritonitis. Peritonitis was associated with a bacterial dose-dependent increase in IL-18 concentrations in peritoneal fluid and plasma. After infection, IL-18 KO mice had significantly more bacteria in the peritoneal lavage fluid and were more susceptible for progression to systemic infection at 6 and 20 h postinoculation than wild-type mice. The relative inability of IL-18 KO mice to clear E. coli from the abdominal cavity was not due to an intrinsic defect in the phagocytosing capacity of their peritoneal macrophages or neutrophils. IL-18 KO mice displayed an increased neutrophil influx into the peritoneal cavity, but these migratory neutrophils were less activate, as reflected by a reduced CD11b surface expression. These data suggest that endogenous IL-18 plays an important role in the early antibacterial host response during E. coli-induced peritonitis.
为了确定内源性白细胞介素-18（IL-18）在腹膜炎中的作用，将IL-18基因缺陷（IL-18 KO）小鼠和野生型小鼠腹腔内注射在脓毒性腹膜炎中最常见的病原体大肠杆菌。腹膜炎与腹腔液和血浆中IL-18浓度的细菌剂量依赖性增加有关。感染后，IL-18 KO小鼠腹腔灌洗液中的细菌明显更多，并且在接种后6小时和20小时比野生型小鼠更容易发展为全身感染。IL-18 KO小鼠从腹腔清除大肠杆菌的相对无能并非由于其腹腔巨噬细胞或中性粒细胞吞噬能力的内在缺陷。IL-18 KO小鼠表现出中性粒细胞向腹腔内的流入增加，但这些迁移的中性粒细胞活性较低，这通过CD11b表面表达的降低得以体现。这些数据表明内源性IL-18在大肠杆菌诱导的腹膜炎早期抗菌宿主反应中起重要作用。
