Interleukin (IL)-33 immunobiology in asthma and airway inflammatory diseases

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.

Keywords:

• IL-33
• allergic asthma
• non-allergic asthma
• lung fibrosis
• asthma-COPD overlap
• repair
• regeneration
• COVID-19

Acknowledgements

The authors thank Lisa Chudomelka with reviewing and editing of manuscript.

Additional information

Funding

JAP receives funding support from National Institute of Environmental Health Sciences grant R01ES019325, National Institute for Occupational Safety and Health grant R01OH012045 and U54OH010162. Both JAP and RG receive funding support from the Central States Center of Agricultural Safety and Health.