Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Innate Immun. 2023 Nov;29(8):161-170. doi: 10.1177/17534259231205959. Epub 2023 Oct 6.
Sepsis is a leading cause of mortality. Plasma cytokine levels may identify those at increased risk of mortality from sepsis. Our aim was to understand how obesity alters cytokine levels during early sepsis and its correlation with survival. Six-week-old C57BL/6 male mice were randomized to control (non-obese) or high fat diet (obese) for 5-7 weeks. Sepsis was induced by cecal ligation and perforation (CLP). Cytokine levels were measured from cheek bleeds 8 h after CLP, and mice were monitored for survival. Other cohorts were sacrificed 1 h after CLP for plasma and tissue. Septic obese mice had higher survival. At 8 h after sepsis, obese mice had higher adiponectin, leptin, and resistin but lower TNFα and IL-6 compared to non-obese mice. When stratified by 24-h survival, adipokines were not significantly different in obese and non-obese mice. TNFα and IL-6 were higher in non-obese, compared to obese, mice that died within 24 h of sepsis. Diet and to sepsis significantly impacted the cecal microbiome. IL-6 is a prognostic biomarker during early sepsis in non-obese and obese mice. A plausible mechanism for the survival difference in non-obese and obese mice may be the difference in gut microbiome and its evolution during sepsis.
脓毒症是导致死亡的主要原因之一。血浆细胞因子水平可能可以识别那些脓毒症死亡率增加的风险。我们的目的是了解肥胖如何在早期脓毒症期间改变细胞因子水平及其与生存的相关性。将 6 周龄 C57BL/6 雄性小鼠随机分为对照组（非肥胖）或高脂肪饮食组（肥胖）5-7 周。通过盲肠结扎和穿孔术（CLP）诱导脓毒症。在 CLP 后 8 小时从脸颊出血中测量细胞因子水平，并监测小鼠的生存情况。其他组在 CLP 后 1 小时牺牲以获得血浆和组织。肥胖的脓毒症小鼠具有更高的存活率。在脓毒症后 8 小时，肥胖小鼠的脂联素、瘦素和抵抗素较高，而 TNFα 和 IL-6 较低。按 24 小时存活率分层时，肥胖和非肥胖小鼠的脂肪因子没有明显差异。在脓毒症后 24 小时内死亡的非肥胖小鼠中，TNFα 和 IL-6 高于肥胖小鼠。饮食和脓毒症对盲肠微生物群有显著影响。IL-6 是脓毒症早期非肥胖和肥胖小鼠的预后生物标志物。非肥胖和肥胖小鼠存活差异的一个合理机制可能是肠道微生物群及其在脓毒症期间的演变差异。
