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(American Journal of Pathology. 2005;166:107-115.)
© 2005 American Society for Investigative Pathology

IL-9 Protects against Bleomycin-Induced Lung Injury

Involvement of Prostaglandins

Mohammed Arras^*, Jamila Louahed, Jean-François Heilier^*, Monique Delos, Frank Brombacher, Jean-Christophe Renauld, Dominique Lison^* and François Huaux^*

From the Unit of Industrial Toxicology and Occupational Medicine^* and the Unit of Experimental Medicine and Ludwig Institute for Cancer Research, Faculty of Medicine, Université Catholique de Louvain, Brussels, Belgium; the Laboratory of Pathology, University Hospital of Mont-Godinne, Yvoir, Belgium; and the University of Cape Town, Cape Town, South Africa

IL-9 is a Th2 cytokine that exerts pleiotropic activities, and might be involved in the regulation of lung inflammatory processes. To characterize the activity of IL-9 on lung injury, we compared the pulmonary responses to bleomycin (blm) in IL-9 transgenic (Tg5) and wild-type (FVB) mice. Following intratracheal instillation of lethal doses of blm, the mortality rate was markedly reduced in Tg5 mice compared to their wild-type counterparts (ie, 25% mortality for Tg5 versus 85% for FVB mice, 21 days after instillation of 0.05U blm/mouse). Histological and biochemical analyses showed that blm induced less lung injury and less epithelial damage in Tg5 as compared to FVB animals. This protection of Tg5 mice was accompanied by an expansion of eosinophils and B cells in the lungs. In addition, TGF-ß and prostaglandin-E2 (PGE2) levels in broncho-alveolar lavage fluid were also increased in transgenic mice. The contribution of B cells and eosinophils to the protective mechanism did not appear essential since eosinophil-deficient (IL-5 KO) and B-deficient (µMT) mice overexpressing IL-9 were also resistant to high doses of blm. We could rule out that TGF-ß was a key factor in the protective effect of IL-9 by blocking this mediator with neutralizing antibodies. Indomethacin treatment, which inhibited PGE2 production in both strains, suppressed the protection in Tg5 mice, supporting the idea that IL-9 controls blm-induced lung injury through a prostaglandin-dependent mechanism.

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