Modulation of ozone-induced airways hyperresponsiveness and inflammation by IL-13

¹ Experimental Studies, Airway Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
² MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UK

^* To whom correspondence should be addressed. E-mail: f.chung{at}imperial.ac.uk.

	Abstract

We determined whether the Th2-derived cytokines, IL-4 and IL-13, can modulate the lung response to ozone exposure.

We exposed IL-13^-/-, IL-4/13^-/- and IL-13-overexpressing mice transgenic (Tg) mice to ozone (3 ppm; 3 hours) 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 airways hyperresponsiveness (AHR) while IL-13Tg mice developed a greater degree of AHR compared to ozone-exposed Wt or IL-13Wt mice, respectively. Ozone caused a time-dependent increase of BAL neutrophils and macrophages in Wt mice, maximal at 20–24 hours, 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 to IL-13Wt mice. Using quantitative real-time PCR, ozone-induced mRNA expression for IL-6 and keratinocyte chemokine (KC) was further enhanced in IL-13^-/- and IL-4/13^-/- mice, and was inhibited in IL-13Tg mice. MIP-3/CCL20 expression was enhanced after ozone exposure in Wt, 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 LPS-induced cytokine (LIX/CXCL5/ENA-78) expression.

IL-13 augments ozone-induced AHR and neutrophilic inflammation, possibly through modulation of certain cytokines induced by ozone exposure.