Thawanaphong Sarita, Nair Aswathi, Volfson Emily, Nair Parameswaran, Mukherjee Manali
Department of Medicine, McMAster University, Hamilton, ON, Canada.
Research Institute of St. Joe's Hamilton, St. Joseph's Healthcare Hamilton, Hamilton, ON, Canada.
Front Med (Lausanne). 2024 Nov 1;11:1486780. doi: 10.3389/fmed.2024.1486780. eCollection 2024.
The role of interleukin-18 (IL-18) and inflammasomes in chronic inflammatory airway diseases, such as asthma and chronic obstructive pulmonary disease (COPD), has garnered significant attention in recent years. This review aims to provide an overview of the current understanding of IL-18 biology, the associated signaling pathways, and the involvement of inflammasome complexes in airway diseases. We explore the multifaceted role of IL-18 in asthma pathophysiology, including its interactions with other cytokines and contributions to both T2 and non-T2 inflammation. Importantly, emerging evidence highlights IL-18 as a critical player in severe asthma, contributing to chronic airway inflammation, airway hyperresponsiveness (AHR), and mucus impaction. Furthermore, we discuss the emerging evidence of IL-18's involvement in autoimmunity and highlight potential therapeutic targets within the IL-18 and inflammasome pathways in severe asthma patients with evidence of infections and airway autoimmune responses. By synthesizing recent advancements and ongoing research, this review underscores the importance of IL-18 as a potential novel therapeutic target in the treatment of severe asthma and other related conditions.
近年来，白细胞介素-18（IL-18）和炎性小体在慢性炎症性气道疾病（如哮喘和慢性阻塞性肺疾病（COPD））中的作用备受关注。本综述旨在概述目前对IL-18生物学、相关信号通路以及炎性小体复合物在气道疾病中的参与情况的理解。我们探讨了IL-18在哮喘病理生理学中的多方面作用，包括其与其他细胞因子的相互作用以及对2型和非2型炎症的贡献。重要的是，新出现的证据表明IL-18是重度哮喘的关键因素，导致慢性气道炎症、气道高反应性（AHR）和黏液嵌塞。此外，我们讨论了IL-18参与自身免疫的新证据，并强调了在有感染和气道自身免疫反应证据的重度哮喘患者中，IL-18和炎性小体途径内的潜在治疗靶点。通过综合近期的进展和正在进行的研究，本综述强调了IL-18作为治疗重度哮喘和其他相关疾病的潜在新治疗靶点的重要性。
