Alarmins differentially modulate airway contraction and relaxation of human small airways.

Alarmins, including Thymic Stromal Lymphopoietin (TSLP) and Interleukins 33 and 25 (IL-33 and IL-25), contribute to the pathophysiology of allergic and nonallergic asthma by evoking exacerbations in response to allergens, viruses, and environmental irritants (as reviewed in [1]). Current evidence shows that inhibiting alarmins reduces symptoms and exacerbations in obstructive lung diseases, including asthma [1]. Preclinical work has largely focused on alarmins' role in modulating airway inflammation, but far less is known about how alarmins regulate airway tone (contraction and relaxation). We posit that IL-33, TSLP, and IL-25 exert distinct effects on airway contraction and relaxation in airways from non-diseased subjects and those with asthma.