Induction of pro-inflammatory mediators by H5N1 infection of primary human lung microvascular endothelial cells

Abstract

Highly pathogenic avian influenza virus H5N1 cause the devastating “bird flu” outbreaks in domestic fowl, but are also occasionally the cause of human disease with a high mortality rate. Infection in birds is systemic with hemorrhages and edema as characteristic symptoms, and virus replication in the endothelium appears to play an important role in pathogenesis, whereas this role for pathogenesis in humans remained uncertain. There is much evidence to suggest that an excessive proinflammatory reaction elicited by H5N1 viruses may be important contributor to H5N1 pathogenesis. In this study we demonstrated that H5N1 enters and replicates in human endothelial cells, but the level of replication is either abortive or too low for infectious particles to be detected. A range of proinflammatory mediators were induced including COX-2, TNF-alpha, IL-1 beta, CXCL10/IP-10, and CCL5/RANTES. Indeed the range of cytokine induction is wider than that of H5N1 infected epithelial cells. Hence lung endothelial cells may not significantly contribute to H5N1 replication as in avian species, however endothelial cells does appears to be important contributor to the proinflammatory cascade that ensues upon H5N1 infection in the respiratory system.