Activation of vascular endothelial cells by IL-<f>1α</f> released by epithelial cells infected with respiratory syncytial virus

Although pulmonary inflammation is a serious, sometimes life-threatening, consequence of respiratory syncytial virus (RSV) infection, the mechanisms involved are not well understood. Since the process of inflammation is initiated by a complex series of events including the activation of specific adhesion molecules on vascular endothelium, we searched for endothelial cell-activating factors released from RSV-infected epithelial cells. We demonstrate here that vascular endothelial cells exposed to culture supernatants from RSV-infected pulmonary epithelial A549 cells are activated to express increased cell surface ICAM-1, and to a lesser extent, VCAM-1 and E-selectin. IL-<f>1α</f> was identified as the predominant endothelial cell-activating factor by pretreating epithelial cell supernatants with anti-IL-<f>1α</f> antibody. The preferential upregulation of endothelial ICAM-1 (relative to VCAM-1 and E-selectin) by RSV-infected epithelial cell supernatants was replicated by recombinant IL-<f>1α</f> thus confirming IL-<f>1α</f> as a major endothelial cell-activating cytokine released by RSV-infected epithelial cells. Il-<f>1α</f> mediated endothelial cell activation is thus a likely contributory event in the initiation of leukocyte inflammation associated with RSV infection. [Copyright &y& Elsevier]