RSV INFECTION OF HUMAN AIRWAY EPITHELIAL-CELLS CAUSES PRODUCTION OF THE BETA-CHEMOKINE RANTES

Infection of airway epithelial cells with respiratory syncytial virus (RSV) results in the production of a restricted number of cytokines, w hich may modulate the inflammatory response to infection. To get a bet ter understanding of epithelial cell-mediated inflammatory processes i n RSV disease, the aim of the present study was to identify the produc tion of mononuclear cell/eosinophil/mast cell inflammatory chemokines [monocyte chemotactic protein (MCP)-1, MCP-3, macrophage inflammatory protein-1 beta, and RANTES] during productive RSV infection in airway epithelial cells. Normal human primary bronchial epithelial cell cultu res, nasal epithelial cell explants, and the BEAS-2B airway epithelial cell line were inoculated with RSV, and chemokine induction was asses sed during the phase of logarithmic increase in infectious virus produ ction. Only RANTES was found to increase in epithelial cell cultures i n an infection-dependent manner. Furthermore, RANTES was released only by RSV-producing cells. To determine whether RANTES was induced by RS V infection in vivo, RANTES was measured in nasal lavage fluids (NLF) from children with RSV-positive and RSV-negative upper respiratory inf ection and children when they were well. RANTES was increased signific antly during RSV infection (128 +/- 38 pg/ml NFL) compared with non-RS V infection (42 +/- 12 pg/ml NFL) and with asymptomatic baseline (13 /- 4 ng/ml NFL) in the same children. Because RANTES is an effective e osinophil and memory T cell chemoattractant and activator and because eosinophil-dominated inflammation is a hallmark of asthmatic airways, RANTES may play a role in the pathogenesis of RSV-induced exacerbation s of airway reactivity and wheezing.