Rago Flavia, Melo Eliza Mathias, Miller Leigh M, Duray Alexis M, Felix Franciel Batista, Vago Juliana Priscila, Gonçalves Ana Paula Faria, Angelo Ana Luiza Pessoa Mendonça, Cassali Giovanni D, Gaetano Monica, Brennan Eoin, Owen Benjamin, Guiry Patrick, Godson Catherine, Alcorn John F, Teixeira Mauro Martins
UMPC Children's Hospital of Pittsburgh.
Universidade Federal de Minas Gerais.
Res Sq. 2024 Jun 13:rs.3.rs-4491036. doi: 10.21203/rs.3.rs-4491036/v1.
Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model.
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.
Mortality rate was assessed up to day 21 and inflammatory parameters were assessed at days 5 and 7.
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 LXA (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.
Therefore, treatment with a lipoxin A 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.
在此，我们评估了一种名为AT-01-KG的合成脂氧素类似物是否会改善甲型流感病毒感染小鼠模型的病程。
小鼠感染甲型H1N1流感病毒，并在感染后第3天用AT-01-KG（1.7毫克/千克/天，腹腔注射）进行治疗。
评估至第21天的死亡率，并在第5天和第7天评估炎症参数。
AT-01-KG减轻了死亡率，在感染后第5天和第7天减少了白细胞浸润和肺损伤。AT-01-KG是一种甲酰肽受体2（在小鼠中称为FPR2/3）激动剂，在FPR2/3基因敲除动物中未观察到保护反应。在用LXA（50毫克/千克/天，腹腔注射，感染后第3 - 6天）治疗的小鼠中，在第7天观察到巨噬细胞重编程，表现为肺中经典活化巨噬细胞减少，替代活化巨噬细胞增加。此外，在治疗小鼠的灌洗液中，凋亡细胞和进行胞葬作用的细胞数量增加。治疗还调节了适应性免疫反应，增加了治疗小鼠肺中抗炎性T细胞（Th2）和调节性T（Tregs）细胞的数量。
因此，用脂氧素A类似物治疗对小鼠甲型流感病毒感染模型有益。该药物减轻了炎症，促进了炎症消退和有益的免疫反应，表明它可能对重症流感患者有用。
