Am. J. Respir. Crit. Care Med., Volume 159, Number 6, June 1999, 1918-1924

Respiratory Syncytical Virus-induced Chemokine Expression in the Lower Airways
Eosinophil Recruitment and Degranulation

A. MARC HARRISON, CYNTHIA A. BONVILLE, HELENE F. ROSENBERG, and JOSEPH B. DOMACHOWSKE

Department of Pediatrics, Divisions of Critical Care and Infectious Diseases, State University of New York Health Science Center at Syracuse, Syracuse, New York; and Laboratory of Host Defenses, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

Characterization of chemokine expression patterns in virus-infected epithelial cells provides important clues to the pathophysiology of such infections. The aim of this study was to determine the chemokine response pattern of respiratory epithelium when infected with respiratory syncytial virus (RSV). Macrophage inflammatory protein-1- (MIP-1-), interleukin-8 (IL-8), and RANTES concentrations were measured from RSV-infected HEp-2, MRC-5, and WI-38 cell culture supernatants daily following infection. Additionally, MIP-1-, IL-8, and RANTES concentrations were measured from lower respiratory secretions obtained from 10 intubated infants (0-24 mo) with RSV bronchiolitis, and from 10 control subjects. Our results indicate that respiratory epithelial cells respond to RSV infection by producing MIP-1-, IL-8, and RANTES. Production of MIP-1- required ongoing viral replication, whereas RANTES and IL-8 could be elicited by inactivated forms of the virus. MIP-1-, RANTES, and IL-8 were also present in lower airway secretions obtained from patients with RSV bronchiolitis. Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN), the eosinophil secretory ribonucleases, were detected in lower airway secretions from RSV-infected patients; ECP concentrations correlated with MIP-1- concentrations (r = 0.93). We conclude that MIP-1- is present in the lower airways during severe RSV disease. The correlation between MIP-1- and ECP concentrations suggests a role for eosinophil degranulation products in the pathogenesis of RSV bronchiolitis.

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