| First Author | Ishikawa Y | Year | 2006 |
| Journal | Int Immunol | Volume | 18 |
| Issue | 6 | Pages | 847-55 |
| PubMed ID | 16611648 | Mgi Jnum | J:109098 |
| Mgi Id | MGI:3625770 | Doi | 10.1093/intimm/dxl021 |
| Citation | Ishikawa Y, et al. (2006) Contribution of IL-18-induced innate T cell activation to airway inflammation with mucus hypersecretion and airway hyperresponsiveness. Int Immunol 18(6):847-55 |
| abstractText | 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 T(h)1 cells in the presence of IL-12. However, our previous reports clearly demonstrated that IL-18 with IL-2 promotes T(h)2 cytokines production from T cells and NK cells. Furthermore, IL-18 with IL-3 stimulates basophils and mast cells to produce T(h)2 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. |
