Interleukin-1 beta augments in vitro alveolar epithelial repair

Biologically active interleukin (IL)-1 beta is present in the pulmonary ede ma fluid obtained from patients with acute lung injury and has been implica ted as an important early mediator of nonpulmonary epithelial wound repair. Therefore, we tested the hypothesis that IL-1 beta would enhance wound rep air in cultured monolayers from rat alveolar epithelial type II cells. IL-1 beta (20 ng/ml) increased the rate of in vitro alveolar epithelial repair by 118 +/- 11% compared with that in serum-free medium control cells (P < 0 .01). IL-1<beta> induced cell spreading and migration at the edge of the wo und but not proliferation. Neutralizing antibodies to epidermal growth fact or (EGF) and transforming growth factor-alpha or inhibition of the EGF rece ptor by tyrphostin AG-1478 or genistein inhibited IL-1 beta -induced alveol ar epithelial repair, indicating that IL-1 beta enhances in vitro alveolar epithelial repair by an EGF- or transforming growth factor-alpha -dependent mechanism. Moreover, the mitogen-activated protein kinase pathway is invol ved in IL-1 beta -induced alveolar epithelial repair because inhibition of extracellular signal-regulated kinase activation by PD-98059 inhibited IL-1 beta -induced alveolar epithelial repair. In conclusion, IL-1 beta augment s in vitro alveolar epithelial repair, indicating a possible novel role for IL-1 beta in the early repair process of the alveolar epithelium in acute lung injury.