Vnitr Lek 2023, 69(6):352-358 | DOI: 10.36290/vnl.2023.070

Alarmins - novel targets for biological therapy

Irena Krčmová, Jakub Novosad

Ústav klinické imunologie a alergologie, Fakultní nemocnice Hradec Králové, Univerzita Karlova v Praze, Lékařská fakulta v Hradci Králové

Biological therapy shows promise for patients with severe asthma, and more biological drugs in clinical trial phases targeted at types of airway inflammation are expected. The choice of biologicals in patients with severe asthma is based on a diagnostic assessment of whether the inflammatory asthma endotype/phenotype is T2-high (i.e., eosinophilic, allergic, or non-allergic) or T2-low (i.e., non-eosinophilic). In clinical practice, three molecules with an anti-eosinophilic access to the cytokine 5 pathway (mepolizumab, benralizumab, reslizumab), a molecule targeted at the IL4/13 receptor (dupilumab), and a molecule binding to immunoglobulin E (omalizumab) are available. The latest molecule to have been introduced in clinical practice is tezepelumab that blocks thymic stromal lymphopoietin, an epithelial alarmin cytokine. Inhibition of alarmins (upstream cytokines) is a novel concept of cytokine blockade. Other molecules intended to inhibit alarmin pathways are also being studied, among which anti‑IL33 itepekimab shows promise. Blockade of epithelial alarmins can be promising for asthma patients with the T2-low type inflammation where an effective biological drug is lacking.

Keywords: asthma, biological therapy, alarmins, TSLP cytokines, IL-33, IL-25.

Accepted: September 21, 2023; Published: October 10, 2023  Show citation