IL-33 in Chronic Respiratory Disease: From Preclinical to Clinical Studies.

IL-33 has been deorphanized as a member of the IL-1 family and has key roles as an alarmin and cytokine with potent capacity to drive type 2 inflammation. This has led to a plethora of studies surrounding its role in chronic diseases with a type 2 inflammatory component. Here, we review the roles of IL-33 in two chronic respiratory diseases, asthma and chronic obstructive pulmonary disease (COPD). We discuss the hallmark and paradigm-shifting studies that have contributed to our understanding of IL-33 biology. We cover animal studies that have elucidated the mechanisms of IL-33 and assessed the role of anti-IL-33 treatment and immunization against IL-33. We highlight key clinical evidence for the potential of targeting increased IL-33 in respiratory diseases including exacerbations, and we outline current clinical trials using an anti-IL-33 monoclonal antibody in asthma patients. Finally, we discuss some of the challenges that have arisen in IL-33 biology and highlight potential future directions in targeting this cytokine in chronic respiratory diseases.