PT - JOURNAL ARTICLE AU - Sawada, Masanori AU - Hoshino, Tomoaki AU - Sakazaki, Yuki AU - Oda, Hanako AU - Takenaka, Shinich AU - Kinoshita, Takashi AU - Imaoka, Haruki AU - Kawayama, Tomotaka AU - Aizawa, Hisamichi TI - Overproduction of IL-18 in the lungs induces IL-13 and IFN-g producing CD4+ T cell in the lungs, and results in airway hyperresponsiveness in Balb/c mice DP - 2011 Sep 01 TA - European Respiratory Journal PG - p3273 VI - 38 IP - Suppl 55 4099 - http://erj.ersjournals.com/content/38/Suppl_55/p3273.short 4100 - http://erj.ersjournals.com/content/38/Suppl_55/p3273.full SO - Eur Respir J2011 Sep 01; 38 AB - We newly established Balb/c background IL-18 transgenic (TG) mice using the human surfactant protein C promoter to drive expression of mature mouse IL-18 cDNA in the lungs. After sensitization on days 0 and 5 with ovalbumin (OVA), mice were challenged with OVA aerosol on day 19. Pulmonary inflammations and airway hyperresponsiveness (AHR) were examined on day 20. We previously reported that constitutive mouse mature IL-18 overproduction in the lungs of C57BL/6 mice induces emphysema (Am J Respir Crit Care Med 2007, 176:49-62). In contrast to C57BL/6 IL-18 TG mice, emphysematous changes were not observed in the lungs of Balb/c IL-18 TG mice. AHR to inhaled acetylcholine were not induced in non-treated Balb/c IL-18 TG mice. However, AHR and airway inflammation accompanied with CD4+ T cells, eosinophils and neutrophils were significantly and greatly increased in OVA-sensitized/challenged Balb/c IL-18 TG mice, when compared with OVA-sensitized/challenged WT Balb/c mice. Moreover, levels of IFN-g and IL-13 in the bronchoalveolar lavage fluid of OVA-sensitized/challenged Balb/c IL-18 TG mice were significantly elevated when compared with OVA-sensitized/challenged WT Balb/c mice. We used anti-CD4 mab or Balb/c IL-18 TG/IL-13 KO mice to examine the role of CD4+ T cells and IL-13 in this Balb/c IL-18 TG mouse. Anti-CD4 mab decrease the level of IL-13 and IFN-g. AHR and pulmonary inflammations were decreased in anti-CD4 mab or Balb/c IL-18 TG/IL-13 KO mice. This study suggested that overproducing IL-18 proteins in the lungs of Balb/c mice induce IL-13 and CD4+ T cells which may involve in the pathogenesis of asthma.