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American Journal of Respiratory and Critical Care Medicine Vol 165. pp. 1540-1545, (2002)
© 2002 American Thoracic Society


Original Article

Interleukin-2–induced Increased Airway Responsiveness and Lung Th2 Cytokine Expression Occur after Antigen Challenge through the Leukotriene Pathway

Sammy Nag, Bouchaib Lamkhioued and Paolo M. Renzi

University of Montreal Hospital Center, Notre-Dame Hospital; and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada

Correspondence and requests for reprints should be addressed to Dr. Paolo M. Renzi, 2065 Alexandre-de-Seve, 8th Floor, Z-8905, Montreal, QC, H2L 2W5, Canada. E-mail: renzip{at}earthlink.net

Previous studies have shown that the allergic late airway response (LR) is dependent on the leukotriene (LT) pathway in Brown Norway (BN) rats. In this same model, interleukin-2 (IL-2) has been shown to increase allergic airway responses without increasing LT production. This study examined the relationship between the upregulation of cellular immunity with IL-2 and the LT pathway in ovalbumin-sensitized BN rats. Airway responsiveness to LTD4 was significantly increased in BN rats pretreated with IL-2 (20,000 U twice a day for 4.5 days). Treatment with montelukast, a cysteinyl LT1 receptor antagonist, blocked IL-2's induced increase of the LR to ovalbumin challenge. When cytokine expression was assessed either by semiquantitative polymerase chain reaction or in situ hybridization, we found that montelukast decreased the amount of IL-4 mRNA expression in the lungs while increasing the amount of interferon-{gamma} mRNA expression 8 hours after challenge. These results indicate that upregulation of cellular immunity with IL-2 can increase the sensitivity of the airways to LTD4 and that inhibition of the LT pathway will block the LR and modulate cytokine expression after antigen challenge.

Key Words: leukotriene D4 • Brown Norway rats • interleukin-4 • interferon-{gamma} • airway inflammation




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Copyright © 2002 American Thoracic Society