IL-33 has 2 forms in COPD: oxidized IL-33 drives mucus dysfunction, while reduced IL-33 recruits inflammatory cells, with implications for mucus plugging.
Interleukin-33 (IL-33) plays 2 distinct roles in
Polverino, Lester and Sue Smith Professor of Medicine at Baylor College of Medicine, described IL-33 as an alarmin released by the bronchial epithelium in response to danger signals such as viral infection or cigarette smoke. Any stimulus triggering the epithelium can prompt this alarm response, she explained. She characterized the cytokine as a potent mediator of both inflammation and structural change in the COPD lung.
The duality stems from 2 molecular forms of IL-33, according to Polverino. The oxidized form drives mucus hyperproduction and dysfunction and alters mucus composition, including the mucins MUC5AC and MUC5B.
Polverino linked the oxidized form to the chronic bronchitis phenotype and identified it as the target of one of the newest biologics in development.
The reduced form, by contrast, acts primarily as a chemoattractant for inflammatory cells, particularly T cells and eosinophils.
Polverino called mucus plugging a major clinical concern, citing evidence linking the number and extent of affected airway segments to mortality and hospitalization in COPD.² Multiple studies over several years have supported this association, and patients with more plugs fare worse, she said.
The relationship between imaging and symptoms is imperfect. Not all patients with CT evidence of mucus plugs report chronic bronchitis symptoms such as productive cough and phlegm, and not all patients with chronic bronchitis show plugs on CT.
Even so, Polverino described mucus plugging as a sensitive measure of inflammation and treatment response in COPD. She pointed to a hyperpolarized MRI trial in which an earlier biologic reduced mucus plugging, alongside symptom improvement and fewer exacerbations.
Because oxidized IL-33 acts directly on mucus formation and composition, Polverino said therapies targeting this pathway are expected to affect both the formation and composition of mucus plugs.
Editor’s Note: This summary transcript has been edited for grammar and clarity using artificial intelligence tools. Polverino had no relevant financial disclosures of note.
