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Am J Physiol Lung Cell Mol Physiol 288: L576-L584, 2005. First published November 24, 2004; doi:10.1152/ajplung.00380.2003
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IL-13 may mediate allergen-induced hyperresponsiveness independently of IL-5 or eotaxin by effects on airway smooth muscle

Seok-Yong Eum,1 Karim Maghni,2 Barbara Tolloczko,2 David H. Eidelman,2 and James G. Martin2

1Department of Microbiology, Yonsei University College of Medicine, Seoul, South Korea; and 2Meakins-Christie Laboratories, Department of Medicine, McGill University, Montreal, Canada

Submitted 5 November 2003 ; accepted in final form 22 November 2004

IL-13 is a mediator of allergen-induced airway hyperresponsiveness (AHR). The aim of this study was to evaluate whether eotaxin and IL-5 were implicated in the effects of IL-13 on allergen-induced AHR or whether IL-13 may exert its effects through direct actions on airway smooth muscle (ASM). To study this question airway inflammation and AHR were induced in mice by sensitization and subsequent challenge on three successive days with ovalbumin. A monoclonal anti-IL-13 antibody administered before each challenge significantly reduced AHR without affecting airway eosinophilia. No changes of mRNA in BAL and lung tissues or protein levels in BAL of IL-5 or eotaxin were found following anti-IL-13 treatment. Combined injection of monoclonal anti-IL-5 and antieotaxin antibodies before each antigen challenge blocked airway eosinophilia but failed to reduce AHR. IL-13 induced calcium transients in cultured murine ASM cells and augmented the calcium and contractile responses of these cells to leukotriene D4. These results suggest that IL-13 plays an important role in allergen-induced AHR and is important in the early phases of the inflammatory process. Its effects on AHR are mediated independently of IL-5 and eotaxin and may involve a direct effect on ASM to augment its responsiveness.

asthma; interleukin-13; airway eosinophilia; calcium signals; mice



Address for reprint requests and other correspondence: J. G. Martin, Meakins-Christie Laboratories, McGill Univ., 3626, rue St-Urbain, Montreal, Qc, Canada H2X 2P2 (E-mail: james.martin{at}mcgill.ca)




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