TY - JOUR T1 - Modulation of ozone-induced airway hyperresponsiveness and inflammation by interleukin-13 JF - European Respiratory Journal JO - Eur Respir J SP - 571 LP - 578 DO - 10.1183/09031936.00121607 VL - 32 IS - 3 AU - A. S. Williams AU - P. Nath AU - S-Y. Leung AU - N. Khorasani AU - A. N. J. McKenzie AU - I. M. Adcock AU - K. F. Chung Y1 - 2008/09/01 UR - http://erj.ersjournals.com/content/32/3/571.abstract N2 - The present study aimed to determine whether the T-helper cell type 2-derived cytokines, interleukin (IL)-4 and -13, can modulate the lung response to ozone exposure. IL-13-/-, IL-4/13-/- and IL-13-overexpressing transgenic (Tg) mice were exposed to ozone (3 ppm; 3 h) or air. Wild-type (Wt) Balb/c mice and transgenic-negative littermates (IL-13Wt) were used as controls for gene-deficient and IL-13Tg mice, respectively. IL-4/13-/- and IL-13-/- mice developed a lesser degree of ozone-induced airway hyperresponsiveness (AHR) while IL-13Tg mice developed a greater degree of AHR compared with ozone-exposed wild-type or IL-13Wt mice, respectively. Ozone caused a time-dependent increase of bronchoalveolar lavage (BAL) neutrophils and macrophages in wild-type mice, maximal at 20–24 h, which was attenuated in the IL-13-/- and IL-4/13-/- mice. In IL-13Tg mice, there was a greater increase in BAL neutrophils after ozone exposure compared with IL-13Wt mice. Using quantitative real-time PCR, ozone-induced mRNA expression for IL-6 and keratinocyte chemokine was further enhanced in IL-13-/- and IL-4/13-/- mice, and was inhibited in IL-13Tg mice. Macrophage inflammatory protein (MIP)-3α/CCL20 expression was enhanced after ozone exposure in wild-type mice, inhibited in IL-13-/- and IL-4/13-/- mice, while in IL-13Tg mice it was enhanced. A similar pattern of expression was observed with lipopolysaccharide-induced cytokine (LIX/CXCL5/ENA-78) expression. In conclusion, interleukin-13 augments ozone-induced airway hyperresponsiveness and neutrophilic inflammation, possibly through modulation of certain cytokines induced by ozone exposure. ER -