PDF(Pubmed)
Abstract：
UNASSIGNED: Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model.
UNASSIGNED: Mice were infected with influenza A/H1N1 and treated with AT-01-KG (1.7 mg/kg/day, i.p.) at day 3 post-infection.
UNASSIGNED: Mortality rate was assessed up to day 21 and inflammatory parameters were assessed at days 5 and 7.
UNASSIGNED: AT-01-KG attenuated mortality, reducing leukocyte infiltration and lung damage at day 5 and day 7 post-infection. AT-01-KG is a Formyl Peptide Receptor 2 (designated FPR2/3 in mice) agonist, and the protective responses were not observed in FPR2/3 -/- animals. In mice treated with LXA4 (50mg/kg/day, i.p., days 3-6 post-infection), at day 7, macrophage reprogramming was observed, as seen by a decrease in classically activated macrophages and an increase in alternatively activated macrophages in the lungs. Furthermore, the number of apoptotic cells and cells undergoing efferocytosis was increased in the lavage of treated mice. Treatment also modulated the adaptive immune response, increasing the number of anti-inflammatory T cells (Th2) and regulatory T (Tregs) cells in the lungs of the treated mice.
UNASSIGNED: Therefore, treatment with a lipoxin A4 analog was beneficial in a model of influenza A infection in mice. The drug decreased inflammation and promoted resolution and beneficial immune responses, suggesting it may be useful in patients with severe influenza.
UNASSIGNED: Mice were infected with influenza A/H1N1 and treated with AT-01-KG (1.7 mg/kg/day, i.p.) at day 3 post-infection.
UNASSIGNED: Mortality rate was assessed up to day 21 and inflammatory parameters were assessed at days 5 and 7.
UNASSIGNED: AT-01-KG attenuated mortality, reducing leukocyte infiltration and lung damage at day 5 and day 7 post-infection. AT-01-KG is a Formyl Peptide Receptor 2 (designated FPR2/3 in mice) agonist, and the protective responses were not observed in FPR2/3 -/- animals. In mice treated with LXA4 (50mg/kg/day, i.p., days 3-6 post-infection), at day 7, macrophage reprogramming was observed, as seen by a decrease in classically activated macrophages and an increase in alternatively activated macrophages in the lungs. Furthermore, the number of apoptotic cells and cells undergoing efferocytosis was increased in the lavage of treated mice. Treatment also modulated the adaptive immune response, increasing the number of anti-inflammatory T cells (Th2) and regulatory T (Tregs) cells in the lungs of the treated mice.
UNASSIGNED: Therefore, treatment with a lipoxin A4 analog was beneficial in a model of influenza A infection in mice. The drug decreased inflammation and promoted resolution and beneficial immune responses, suggesting it may be useful in patients with severe influenza.
摘要：
目的：这里，我们评估了合成的脂氧素模拟物，指定AT-01-KG，将改善小鼠模型中甲型流感感染的过程。
方法：小鼠感染甲型H1N1流感并用AT-01-KG（1.7mg/kg/天，i.p.)在感染后第3天。方法在第21天评估死亡率，在第5天和第7天评估炎症参数。结果AT-01-KG减毒死亡率，减少感染后第5天和第7天的白细胞浸润和肺损伤。AT-01-KG是甲酰基肽受体2（在小鼠中指定为FPR2/3）激动剂，在FPR2/3-/-动物中未观察到保护性反应。在用LXA4治疗的小鼠中（50mg/kg/天，i.p.,感染后3-6天），在第7天，观察到巨噬细胞重编程，从经典激活的巨噬细胞的减少和肺中交替激活的巨噬细胞的增加可以看出。此外，在经处理的小鼠的灌洗中,凋亡细胞和经历过细胞凋亡的细胞数量增加.治疗还调节了适应性免疫反应，增加治疗小鼠肺中抗炎T细胞(Th2)和调节性T细胞(Tregs)的数量。因此，结论，用脂氧素A4类似物治疗在小鼠甲型流感感染模型中是有益的。该药物减少了炎症，促进了消退和有益的免疫反应，提示它可能对严重流感患者有用。
方法：小鼠感染甲型H1N1流感并用AT-01-KG（1.7mg/kg/天，i.p.)在感染后第3天。方法在第21天评估死亡率，在第5天和第7天评估炎症参数。结果AT-01-KG减毒死亡率，减少感染后第5天和第7天的白细胞浸润和肺损伤。AT-01-KG是甲酰基肽受体2（在小鼠中指定为FPR2/3）激动剂，在FPR2/3-/-动物中未观察到保护性反应。在用LXA4治疗的小鼠中（50mg/kg/天，i.p.,感染后3-6天），在第7天，观察到巨噬细胞重编程，从经典激活的巨噬细胞的减少和肺中交替激活的巨噬细胞的增加可以看出。此外，在经处理的小鼠的灌洗中,凋亡细胞和经历过细胞凋亡的细胞数量增加.治疗还调节了适应性免疫反应，增加治疗小鼠肺中抗炎T细胞(Th2)和调节性T细胞(Tregs)的数量。因此，结论，用脂氧素A4类似物治疗在小鼠甲型流感感染模型中是有益的。该药物减少了炎症，促进了消退和有益的免疫反应，提示它可能对严重流感患者有用。
