The goal of this study was to determine time courses of upregulation of several chemokines in nasal secretions after inoculation of human subjects with a low dose of live respiratory syncytial virus (RSV). Healthy, nonsmoking young adults were admitted to an inpatient clinical research unit. After baseline studies, subjects were nasally inoculated with approximately 10(3) plaque-forming units of RSV (strain A2), followed by daily nasal lavages. Nasal lavage fluid (NLF) was assayed for chemokines by specific ELISA. Of 10 subjects inoculated with RSV, 3 developed clinical symptoms of upper respiratory infection and also shed virus. Among infected subjects, there was a transient postinoculation increase in interleukin-8 (IL-8) in NLF to an average of 2.7-fold compared to baseline, followed by a prolonged increase (maximum mean 5.4-fold) during virus shedding. RANTES, MIP-1alpha, and MCP-1 all increased during virus shedding only (maximum mean increases of 5.3-fold, 13-fold, and 7.2-fold, respectively). Semiquantitative RT-PCR in brushed nasal epithelial cells on day 6 after inoculation suggested upregulation of RANTES, but not IL-8, mRNA during virus shedding. We conclude that chemokines IL-8, RANTES, MIP-1alpha, and MCP-1 are all increased in nasal secretions in human RSV infection at the time of virus shedding and symptomatic illness and that the epithelium lining the nasal turbinate contributes to the increase in RANTES.
Copyright 2000 Academic Press.