Alpha1-antitrypsin (AAT) is a serum protease inhibitor that rises during inflammation and healthy pregnancies. Plasma-derived AAT, indicated for genetic AAT deficiency, is presently being explored for additional medical indications. Unlike corticosteroids, some anti-inflammatory activities of AAT involve NF-κB–dependent outcomes, e.g., induction of IL-1R antagonist. AAT activities were compared to dexamethasone (DEX), using various in-vitro cells assays, animal studies, and NF-κB–p65 localization and activity studies. Results demonstrate a cytokine shift towards resolution in AAT-treated cells, as opposed to pan-suppression in DEX-treated cells. AAT enhanced, while DEX suppressed LPS-induced IL-1Ra production and re-epithelialization. When drugs were combined, AAT allowed the immunosuppressive DEX activities, while DEX at medium to high levels antagonized beneficial AAT effects. Interestingly, lower levels of DEX maintained the immunosuppressive effect, while allowing upregulation of IL-1Ra. Therefore, AAT may represent a distinct endogenous anti-inflammatory, resolution-promoting agent that may improve tissue well-being while preventing undesired corticostroids side effects.

Alpha1-抗胰蛋白酶（AAT）是一种血清蛋白酶抑制剂，在炎症和健康怀孕期间会升高。针对遗传性AAT缺乏症的血浆来源的AAT，目前正在探索用于其他医学适应症。与皮质类固醇不同，AAT的某些抗炎活性涉及依赖NF-κB的结果，例如诱导IL-1R拮抗剂。使用各种体外细胞测定，动物研究以及NF-κB-p65定位和活性研究，将AAT活性与地塞米松（DEX）进行了比较。结果表明，与经DEX处理的细胞的泛抑制相反，在经AAT处理的细胞中，细胞因子向着分辨率的方向转移。AAT增强，而DEX抑制LPS诱导的IL-1Ra产生和上皮再生。当药物合用时，AAT允许免疫抑制DEX活性，而中高水平的DEX则拮抗了AAT的有益作用。有趣的是，较低水平的DEX保持了免疫抑制作用，同时允许IL-1Ra上调。因此，AAT可能代表一种独特的内源性抗炎，促进分辨率的药物，可以改善组织的健康状况，同时防止不良的皮质类固醇激素副作用。