[Alarmins and anti-alarmin biologics in asthma]

Alarmins are endogenous, constitutively expressed, chemotactic, and immune activating proteins/peptides that are released as a result of degranulation, cell injury or death, or in response to immune induction. Alarmins are involved in a variety of processes including antimicrobial gene expression regulation, cellular homeostasis, wound healing, inflammation, allergy, autoimmunity and oncogenesis. IL-25, IL-33, thymic stromal lymphopoietin (TSLP) are airway epithelial-derived alarmins and the characteristics of alarmins are that they are rapidly released after nonprogrammed cell death, they activate the immune cells. It is thought that the inhibition of the effects of alarmin on the immune system may be useful in the treatment of asthma. The effects of anti-IL-25 (Brodalumab) and anti-TSLP (Tezepelumab) treatments on asthmatic patients were investigated for that purpose. Brodalumab provided limited benefit only in the asthmatic group with high reversibility. Tezepelumab was found to be the first biological drug to have significant positive effect on two important indicators of asthmatic inflammation such as blood eosinophils and nitric oxide fraction in exhaled air. The effect of anti-IL-33 on airway inflammation was shown in animal experiments and anti-IL-33 was found to be protective by reducing eosinophilia, inflammatory cytokines, airway hypersensitivity. In this review, we aimed to summarize the role of alarmines in the pathogenesis of asthma and the results of studies with anti-alarmin biologics.