In the context of asthma pathophysiology, especially during exacerbations and airway inflammation, interleukin-33 (IL-33) holds a pivotal role. This study delves into elucidating the impact of IL-33 on ferroptosis during asthma exacerbations. Through comprehensive transcriptomic and proteomic analyses, IL-33 and GPX4 emerged as crucial regulators in this intricate process. In vitro experiments showcased the remarkable anti-inflammatory and ferroptosis-mitigating effects of an IL-33 antibody in IL-13-induced BEAS-2B cells. Subsequent in vivo validation in mice underscored the ability of the IL-33 antibody to diminish inflammatory responses, enhance GPX4 expression, and ameliorate asthma symptoms. These compelling findings suggest that the IL-33 antibody holds promise in suppressing ferroptosis, alleviating inflammation, and modulating GPX4 expression, thereby proposing novel therapeutic strategies for managing asthma exacerbations by targeting the IL-33 and ferroptosis pathways.

Keywords: Airway inflammation response; Allergic asthma; Ferroptosis; GPX4; IL-33; Inflammation; Therapeutic Targets.

Copyright © 2025. Published by Elsevier Inc.

在哮喘病理生理学的背景下，特别是在哮喘加重和气道炎症期间，白细胞介素-33（IL-33）扮演着至关重要的角色。本研究深入探讨了IL-33对哮喘加重期间铁死亡的影响。通过全面的转录组学和蛋白质组学分析，IL-33和GPX4被确定为这一复杂过程中的关键调节因子。体外实验展示了IL-13诱导的BEAS-2B细胞中使用IL-33抗体所产生的显著抗炎作用以及减轻铁死亡的效果。随后在小鼠体内验证试验进一步强调了IL-33抗体能够减少炎症反应、增强GPX4表达并改善哮喘症状的能力。这些令人信服的研究结果表明，IL-33抗体有望通过抑制铁死亡、缓解炎症和调节GPX4表达来提出新的治疗策略，从而针对IL-33和铁死亡通路管理哮喘加重。

关键词： 气道炎症反应；过敏性哮喘；铁死亡；GPX4；IL-33；炎症；治疗靶点。