title: Increased hyperoxia-induced mortality and acute lung injury in IL-13 null mice.
abstract: IL-13 is a critical effector at sites of Th2 inflammation and remodeling. As a result, anti-IL-13-based therapies are being actively developed to treat a variety of diseases and disorders. However, the beneficial effects of endogenous IL-13 in the normal and diseased lung have not been adequately defined. We hypothesized that endogenous IL-13 is an important regulator of oxidant-induced lung injury and inflammation. To test this hypothesis, we compared the effects of 100% O(2) in mice with wild-type and null IL-13 loci. In this study, we demonstrate that hyperoxia significantly augments the expression of the components of the IL-13R, IL-13Ralpha1, and IL-4Ralpha. We also demonstrate that, in the absence of IL-13, hyperoxia-induced tissue inflammation is decreased. In contrast, in the IL-13 null mice, DNA injury, cell death, caspase expression, and activation and mortality are augmented. Interestingly, the levels of the cytoprotective cytokines vascular endothelial cell growth factor, IL-6, and IL-11 were decreased in the bronchoalveolar lavage fluid. These studies demonstrate that the expression of the IL-13R is augmented and that the endogenous IL-13-IL-13R pathway contributes to the induction of inflammation and the inhibition of injury in hyperoxic acute lung injury.
authors.affiliation: Division of Perinatal Medicine, Yale University School of Medicine, Department of Pediatrics, Children's Hospital, New Haven, CT 06520, USA.
authors.forename: Vineet
authors.initials: V
authors.lastname: Bhandari
authors.forename: Rayman
authors.initials: R
authors.lastname: Choo-Wing
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Homer
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
mesh_terms: D000818:Animals; D017209:Apoptosis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D018496:Hyperoxia / Q000401:mortality*; D007249:Inflammation / Q000209:etiology; D017370:Interleukin-11 / Q000032:analysis; D018793:Interleukin-13 / Q000032:analysis / Q000172:deficiency / Q000502:physiology*; D015850:Interleukin-6 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D053660:Receptors, Interleukin-13 / Q000032:analysis; D012128:Respiratory Distress Syndrome / Q000209:etiology* / Q000517:prevention & control; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: D017370:Interleukin-11; D018793:Interleukin-13; D015850:Interleukin-6; D019253:Proto-Oncogene Proteins c-bcl-2; D053660:Receptors, Interleukin-13; D042461:Vascular Endothelial Growth Factor A; D051028:bcl-2-Associated X Protein