ALUNG July 21/1

Vlahakis, Nicholas E., Mark A. Schroeder, Andrew H. Limper, and Rolf D. Hubmayr. Stretch induces cytokine release by alveolar epithelial cells in vitro. Am. J. Physiol. 277 (Lung Cell. Mol. Physiol. 21): L167–L173, 1999.—Mechanical ventilation can injure the lung, causing edema and alveolar inflammation. Interleukin-8 (IL-8) plays an important role in this inflammatory response. We postulated that cyclic cell stretch upregulates the production and release of IL-8 by human alveolar epithelium in the absence of structural cell damage or paracrine stimulation. To test this hypothesis, alveolar epithelial cells (A549 cells) were cultured on a deformable silicoelastic membrane. When stretched by 30% for up to 48 h, the cells released 49 6 34% more IL-8 (P , 0.001) than static controls. Smaller deformations (20% stretch) produced no consistent increase in IL-8. Stretch of 4 h duration increased IL-8 gene transcription fourfold above baseline. Stretch had no effect on cell proliferation, cell viability as assessed by 51Cr release assay, or the release of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-a. We conclude that deformation per se can trigger inflammatory signaling and that alveolar epithelial cells may be active participants in the alveolitis associated with ventilator-induced lung injury.