Contribution of IL-18-induced innate T cell activation to airway inflammation with mucus hypersecretion and airway hyperresponsiveness
- PMID: 16611648
- DOI: 10.1093/intimm/dxl021
Contribution of IL-18-induced innate T cell activation to airway inflammation with mucus hypersecretion and airway hyperresponsiveness
Abstract
Human bronchial asthma is characterized by airway hyperresponsiveness (AHR), eosinophilic airway inflammation, mucus hypersecretion and high serum level of IgE. IL-18 was originally regarded to induce T(h)1-related cytokines from Th1 cells in the presence of IL-12. However, our previous reports clearly demonstrated that IL-18 with IL-2 promotes Th2 cytokines production from T cells and NK cells. Furthermore, IL-18 with IL-3 stimulates basophils and mast cells to produce Th2 cytokines. Thus, we examined the capacity of IL-2 and IL-18 to induce AHR, airway eosinophilic inflammation and goblet cell metaplasia. Intranasal administration of IL-2 and IL-18 induces AHR, mucus hypersecretion and eosinophilic inflammation in the lungs of naive mice. CD4+ T cells are prerequisite for this IL-2 plus IL-18-induced bronchial asthma, because CD4+ T cells-depleted or Rag-2-deficient (Rag-2-/-) mice did not develop bronchial asthma after IL-2 plus IL-18 treatment. Both STAT6-/- mice and IL-13-neutralized wild-type mice failed to develop AHR, goblet cell metaplasia and airway eosinophilic inflammation, while IL-4-/- mice almost normally developed, suggesting that IL-13 is a major causative factor and IL-4 mainly enhances the degree of AHR and eosinophilic inflammation. Both IL-4 and IL-13 equally induce eotaxin in mouse embryonic fibroblasts. However, only IL-13 blockade inhibited asthma symptoms, suggesting that IL-13 but not IL-4 is produced abundantly and plays a critical role in the pathogenesis of bronchial asthma in this model. As airway epithelial cells store robust IL-18, IL-18 might be critically involved in pathogen-induced bronchial asthma, in which pathogens stimulate epithelial cells to produce IL-18 without IL-12 induction.
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