Ongoing Study of IL-23 in Asthma May Yield More Treatment Options

A better understanding of the complex interplay between interleukin (IL)-23 and airway inflammation in patients with asthma may yield future treatment options beyond traditional anti-type 2 inflammatory therapies, suggests an editorial published in Expert Review of Clinical Immunology.

“Increasingly, asthma is recognized as a clinically heterogenous disease—both in terms of phenotypic presentation as well as molecular basis of inflammation—with subsets of steroid-unresponsive patients that have predominantly neutrophilic, rather than eosinophilic, inflammation,” wrote first author Ashley Y Wu, MD, and corresponding author R Stokes Peebles, MD, of Vanderbilt University School of Medicine, Nashville, Tennessee.

A novel target for asthma therapy generating plenty of interest is modulating IL-23 and its downstream IL-23/CD4+ T helper 17 (Th17) axis, but results from animal and human studies have been mixed, the editorial explained. Nevertheless, there is hope that lessons learned may eventually result in targeted therapies that may benefit certain patients.

“Perhaps, in select patients with severe treatment-resistant disease (eg, characterized by sputum neutrophilia and peripheral eosinophilia), a dual inhibition of type 2 and type 3 inflammatory responses with combined IL-13 and IL-17 blockade may be necessary to achieve disease remission,” the authors wrote. “Or perhaps, without a current ability to precisely phenotype asthma patients, a complete IL-23 or IL-17 blockade is too heavy-handed.”

If any patients stand to benefit from a singular Th17 blockade, the authors suspect it will be those with high sputum neutrophils and without a history of atopy.

“Ongoing research on underlying immunological pathways and the role of epithelial cells will allow for a more nuanced understanding of interplay between immune cells and their environment in severe asthma patients that is needed to guide therapy,” the authors advised.

Reference: 
Wu AY, Peebles RS. The emerging role of IL-23 in asthma and its clinical implications. Expert Rev Clin Immunol. 2023;19(1):1-5. doi:10.1080/1744666X.2023.2125380