The role of the NLRP3 inflammasome in the pathogenesis of bronchial asthma: inflammatory mechanisms and emerging therapeutic perspectives

This article explores the pathophysiological mechanisms and therapeutic potential for treating bronchial asthma, a significant global public health issue. Immune-mediated inflammation is central to asthma pathogenesis and involves the formation of inflammasomes—molecular complexes that regulate inflammatory responses. The NLRP3 inflammasome plays a pivotal role in disease progression by interacting with allergens and triggering signaling cascades that lead to the production of proinflammatory cytokines, such as interleukin-1β (IL-1β) and IL-18. These cytokines recruit immune cells, including mast cells, eosinophils, and T lymphocytes, which contribute to airway inflammation, hyperresponsiveness, and bronchial obstruction. The article discusses asthma phenotypes, including infection-induced and atopic asthma, and the link between NLRP3 inflammasome activation and impaired lung function, steroid resistance, and neutrophilic inflammation. Special attention is given to the cellular and molecular pathways involved in the inflammatory response, including interactions between the inflammasome and T helper cells, macrophages, eosinophils, and mast cells. These interactions lead to the release of histamine, heparin, lysosomal enzymes, reactive oxygen species, nitric oxide, prostaglandins, and leukotrienes. Inflammatory mediators such as IL-4, IL-5, and IL-13 contribute to airway remodeling, mucus hypersecretion, and bronchospasm. Additionally, inflammasome activation can impair epithelial barrier integrity, further exacerbating allergic inflammation. The article emphasizes the chronic changes in the bronchial tree caused by sustained inflammation and highlights the importance of regulating inflammasome activity. In particular, the selective NLRP3 inflammasome inhibitor MCC950 has demonstrated efficacy in reducing inflammation and shows promise as a novel therapeutic approach. The article concludes that integrating inflammasome research into clinical practice (particularly through the use of targeted therapies such as MCC950) may transform the approach to asthma treatment. This underscores the importance of transitioning toward personalized medicine in the management of chronic inflammatory diseases such as bronchial asthma.