Department of Pediatrics, University of Pittsburgh, University of Pittsburgh Medical Center, Children's Hospital of Pittsburgh, Pittsburgh, PA.
Division of Allergy, Immunology and Rheumatology, Department of Medicine, University of Rochester, Rochester, NY.
Immunohorizons. 2023 Dec 1;7(12):861-871. doi: 10.4049/immunohorizons.2300077.
Influenza is a highly contagious, acute respiratory disease that causes significant public health and economic threats. Influenza infection induces various inflammatory mediators, IFNs, and recruitment of inflammatory cells in the host. This inflammatory "cytokine storm" is thought to play a role in influenza-induced lung pathogenesis. Empagliflozin is a drug primarily used to lower blood glucose in type II diabetes patients by inhibiting the sodium-glucose cotransporter-2 (SGLT-2) found in the proximal tubules in the kidneys. In this study, we have investigated the effects of empagliflozin on the pulmonary immune response to influenza infection. C57BL/6 mice (wild type) were infected with influenza A/PR/8/34 and treated with empagliflozin, and the disease outcomes were analyzed. Empagliflozin treatment decreased the expression of the inflammatory cytokines IL-1β, IL-6, and CCL2; the percentage of inflammatory monocytes and inducible NO synthase-positive macrophages; and IFN response genes Stat1 and CXCL9 during influenza infection. Further, empagliflozin treatment decreases the expression of IL-6, CCL2, and CCL5 in RAW264.7 macrophages and bone marrow-derived macrophages. However, empagliflozin treatment increased influenza viral titer during infection. Despite fostering an increased viral burden, treatment with empagliflozin decreases the mortality in wild type and high fat diet-induced atherosclerotic LDLR-/- mice. Based on our findings, empagliflozin may have therapeutic implications for use in patients to prevent lung damage and acute respiratory illness.
流感是一种高度传染性的急性呼吸道疾病，对公共卫生和经济造成重大威胁。流感感染会诱导宿主产生各种炎症介质、IFNs 和炎症细胞的募集。这种炎症“细胞因子风暴”被认为在流感引起的肺部发病机制中起作用。恩格列净是一种主要用于降低 2 型糖尿病患者血糖的药物，通过抑制肾脏近端小管中的钠-葡萄糖协同转运蛋白-2（SGLT-2）。在这项研究中，我们研究了恩格列净对流感感染后肺部免疫反应的影响。C57BL/6 小鼠（野生型）感染流感 A/PR/8/34 并接受恩格列净治疗，分析疾病结局。恩格列净治疗降低了流感感染时炎症细胞因子 IL-1β、IL-6 和 CCL2 的表达；炎症单核细胞和诱导型一氧化氮合酶阳性巨噬细胞的百分比；以及 IFN 反应基因 Stat1 和 CXCL9。此外，恩格列净治疗降低了 RAW264.7 巨噬细胞和骨髓来源的巨噬细胞中 IL-6、CCL2 和 CCL5 的表达。然而，恩格列净治疗在感染期间增加了流感病毒滴度。尽管恩格列净治疗增加了病毒载量，但它降低了野生型和高脂肪饮食诱导的动脉粥样硬化 LDLR-/- 小鼠的死亡率。基于我们的发现，恩格列净可能对预防肺部损伤和急性呼吸道疾病的患者具有治疗意义。
