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Modulation of ozone-induced airway hyperresponsiveness and inflammation by interleukin-13

¹ Experimental Studies, Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, and ² The Medical Research Council, Laboratory of Molecular Biology, Cambridge, UK.

CORRESPONDENCE: K. F. Chung, Experimental Studies, Airway Disease Section, National Heart & Lung Institute, Guy Scadding Building, Dovehouse St., London SW3 6LY, UK. Fax: 44 2073518126. E-mail: f.chung{at}imperial.ac.uk

Keywords: Airways hyperresponsiveness, interleukin-4, interleukin-13, neutrophils, ozone

Received: September 14, 2007
Accepted March 28, 2008

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)-3/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.