Interleukin-33 mejora la respuesta y la liberación de mediadores de mastocitos en vías aéreas pequeñas humanas...

Concomitant exposure to interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and IL-25 augments antigen-induced contractions of isolated human small bronchi through enhanced mast cell reactivity.

The individual contribution of alarmins was tested in antigen-induced airway hyperresponsiveness and hyperosmolarity-induced responses evoked by mannitol, a surrogate model of exercise-induced bronchoconstriction.

Intact segments of small airways, isolated from fresh human lung tissue, were incubated with IL-33, TSLP, IL-25, or buffer control for 48 hours. Contractile responses to anti-IgE or mannitol were then assessed using myograph systems. Mast cell degranulation and mediator release were analysed both from the bronchial segments and from isolated primary human lung mast cells (HLMCs) as well as from the human mast cell line LAD2.

IL-33 increased contractile force (E_max) to anti-IgE and hyperosmolar mannitol by 62% and 78%, respectively. IL-33 also doubled antigen-IgE-induced prostaglandin (PG)D₂ release from bronchial segments as well as enhanced degranulation, cysteinyl-leukotriene (cysLT) and PGD₂ release from isolated HLMCs stimulated by anti-IgE or mannitol. In contrast, TSLP and IL-25 had no effect on contraction, degranulation, or mediator release in response to either stimulus.

IL-33, but not TSLP or IL-25, enhances bronchoconstriction in human small bronchi by amplifying mast cell activation and mediator release in response to both antigen and hyperosmolar challenge.