| First Author | Ward NS | Year | 2000 |
| Journal | Am J Respir Cell Mol Biol | Volume | 22 |
| Issue | 5 | Pages | 535-42 |
| PubMed ID | 10783124 | Mgi Jnum | J:146051 |
| Mgi Id | MGI:3836548 | Doi | 10.1165/ajrcmb.22.5.3808 |
| Citation | Ward NS, et al. (2000) Interleukin-6-induced protection in hyperoxic acute lung injury. Am J Respir Cell Mol Biol 22(5):535-42 |
| abstractText | Hyperoxic lung injury is commonly encountered in patients who require treatment with high concentrations of inspired oxygen. To determine whether interleukin (IL)-6 is protective in oxygen toxicity, we compared the effects of 100% O(2) in transgenic mice that overexpress IL-6 in the lung and transgene (-) controls. IL-6 markedly enhanced survival, with 100% of transgene (-) animals dying within 72 to 96 h, 100% of transgene (+) animals living for more than 8 d and more than 90% of transgene (+) animals living longer than 12 d. This protection was associated with markedly diminished alveolar-capillary protein leak, endothelial and epithelial membrane injury, and lung lipid peroxidation. Hyperoxia also caused cell death with DNA fragmentation in the lungs of transgene (-) animals and IL-6 markedly diminished this cytopathic response. The protective effects of IL-6 were not associated with significant alterations in the activities of copper/ zinc superoxide dismutase (SOD) or manganese SOD. They were, however, associated with the enhanced accumulation of the cell-death inhibitor Bcl-2, but not the cell-death stimulator BAX, and with the heightened accumulation of the cell-death regulator tissue inhibitor of metalloproteinase-1 (TIMP-1). These studies demonstrate that IL-6 markedly diminishes hyperoxic lung injury and that this protection is associated with a marked diminution in hyperoxia-induced cell death and DNA fragmentation. They also demonstrate that this protection is not associated with significant alterations in SOD activity, but is associated with the induction of Bcl-2 and TIMP-1. |
