Department of Cell Biology and Neuroscience, Rowan University - School of Osteopathic Medicine, Stratford, NJ, USA.
Department of Cell Biology and Neuroscience, Rowan University - School of Osteopathic Medicine, Stratford, NJ, USA; Biomarker Discovery Center, New Jersey Institute of Successful Aging, Rowan University - School of Osteopathic Medicine, Stratford, NJ, USA.
Prostaglandins Other Lipid Mediat. 2022 Apr;159:106617. doi: 10.1016/j.prostaglandins.2022.106617. Epub 2022 Jan 8.
In the development of sepsis, there is early, massive inflammation which can lead to multiple organ failure. Later there is an immunosuppressed phase where the host is susceptible to secondary infections or is unable to clear existing infection. Specialized Pro-resolving Mediators (SPMs) are endogenously produced lipids which resolve infection by decreasing bacteria load and reducing systemic inflammatory response. There has been little work studying if SPMs given late, can promote host defense. We examined if an SPM, Resolvin D2 (RvD2) could promote host defense in a 2-hit mouse model of cecal ligation and puncture (CLP) sepsis and secondary Pseudomonas aeruginosa lung infection. RvD2 given 48 h after mild CLP (1st hit), increased gene expression of Toll-like receptor-2 (TLR-2) and alveolar macrophage/monocyte phagocytic ability compared to CLP mice given saline vehicle. In this model, RvD2 did not affect plasma IL-6 or IL-10. These effects induced by RvD2, lowered lung bacterial load and decreased mortality after the secondary infection of Pseudomonas aeruginosa (2nd hit). Splenic T-cell numbers were also increased in RvD2 treated mice compared to saline vehicle treated animals. The results suggest that RvD2 promoted mechanisms of host defense in a 2-hit model sepsis and secondary lung infection.
在脓毒症的发展过程中，早期会出现大量炎症，可能导致多器官衰竭。随后，宿主会进入免疫抑制阶段，容易发生二次感染或无法清除现有感染。特异性促解决介质（SPM）是内源性产生的脂质，通过降低细菌负荷和减少全身炎症反应来解决感染。目前关于晚期给予 SPM 是否能促进宿主防御的研究较少。我们研究了一种 SPM，即 Resolvin D2（RvD2），能否在盲肠结扎和穿刺（CLP）脓毒症的双打击小鼠模型和继发性铜绿假单胞菌肺部感染中促进宿主防御。与给予生理盐水载体的 CLP 小鼠相比，RvD2 在轻度 CLP（第 1 次打击）后 48 小时给予，可增加 Toll 样受体 2（TLR-2）的基因表达和肺泡巨噬细胞/单核细胞的吞噬能力。在该模型中，RvD2 对血浆 IL-6 或 IL-10 没有影响。RvD2 诱导的这些作用降低了肺部细菌负荷，并降低了继发性铜绿假单胞菌感染后的死亡率。与给予生理盐水载体的动物相比，RvD2 处理的小鼠脾脏 T 细胞数量也增加了。结果表明，RvD2 在双打击模型脓毒症和继发性肺部感染中促进了宿主防御机制。
