Abstract
OBJECTIVE: Identify key features of IL-33 immunobiology important in allergic and nonallergic airway inflammatory diseases and potential therapeutic strategies to reduce disease burden. DATA SOURCES: PubMed, clinicaltrials.gov. STUDY SELECTIONS: A systematic and focused literature search was conducted of PubMed from March 2021 to December 2021 using keywords to either PubMed or BioMed Explorer including IL-33/ST2, genetic polymorphisms, transcription, translation, post-translation modification, nuclear protein, allergy, asthma, and lung disease. Clinical trial information on IL-33 was extracted from clinicaltrials.gov in August 2021. RESULTS: In total, 72 publications with relevance to IL-33 immunobiology and/or clinical lung disease were identified (allergic airway inflammation/allergic asthma n = 26, non-allergic airway inflammation n = 9, COPD n = 8, lung fibrosis n = 10). IL-33 levels were higher in serum, BALF and/or lungs across inflammatory lung diseases. Eight studies described viral infections and IL-33 and 4 studies related to COVID-19. Mechanistic studies (n = 39) including transcript variants and post-translational modifications related to the immunobiology of IL-33. Single nucleotide polymorphism in IL-33 or ST2 were described in 9 studies (asthma n = 5, inflammatory bowel disease n = 1, mycosis fungoides n = 1, ankylosing spondylitis n = 1, coronary artery disease n = 1). Clinicaltrials.gov search yielded 84 studies of which 17 were related to therapeutic or biomarker relevance in lung disease. CONCLUSION: An integral role of IL-33 in the pathogenesis of allergic and nonallergic airway inflammatory disease is evident with several emerging clinical trials investigating therapeutic approaches. Current data support a critical role of IL-33 in damage signaling, repair and regeneration of lungs.