IL-13 stimulates vascular endothelial cell growth factor and protects against hyperoxic acute lung injury

Hyperoxia is an important cause of acute lung injury. To determine whether IL-13 is protective in hyperoxia, we compared the survival in 100% O-2 of t ransgenic mice that overexpress IL-13 in the lung and of nontransgenic litt ermate controls. IL-13 enhanced survival in 100% O-2. One hundred percent o f nontransgenic mice died in 4-5 days, whereas 100% of IL-13-overexpressing mice lived for more than 7 days, and many lived 10-14 days. IL-13 also sti mulated VEGF accumulation in mice breathing room air, and it interacted wit h 100% O-2 to increase VEGF accumulation further. The 164-amino acid isofor m was the major VEGF moiety in bronchoalveolar lavage from transgenic mice in room air, whereas the 120- and 188-amino acid isoforms accumulated in th ese mice during hyperoxia. In addition, antibody neutralization of VEGF dec reased the survival of IL-13-overexpressing mice in 100% O-2. These studies demonstrate that IL-13 has protective effects in hyperoxic acute lung inju ry. They also demonstrate that IL-13, alone and in combination with 100% O- 2, stimulates pulmonary VEGF accumulation, that this stimulation is isoform -specific, and that the protective effects of IL-13 are mediated, in part, by VEGF.