Elevated cytokine concentrations in the nasopharyngeal and tracheal secretions of children with respiratory syncytial virus disease

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Abstract
Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract disease in infants. The role of inflammatory mediators in the pathogenesis of RSV disease is not well-understood. The present study was designed (1) to determine whether RANTES (regulated on activation, normal T cell expressed and presumably secreted), macrophage-inflammatory protein-1-alpha (MIP-1-alpha), interleukin (IL)-6, IL-8 and IL-10 can be detected in respiratory secretions of children with RSV infection and (2) to assess whether the concentrations of these cytokines in respiratory secretions correlate with white blood cell (WBC) counts and RSV concentrations and with disease severity. During the 1996 to 1997 RSV season, we studied prospectively 14 intubated and 14 nonintubated children hospitalized with RSV disease. Nasal wash (NW) and tracheal aspirate (TA) samples were obtained from intubated patients on Hospital Days 1, 3 and 5. NW samples were obtained from nonintubated patients on hospital days 1 and 3. Seven healthy children undergoing elective surgery served as controls. All samples were analyzed for: (1) WBC and differential counts; (2) concentrations of RANTES, MIP-1-alpha, IL-6, IL-8 and IL-10; and (3) quantitative RSV cultures, except in control patients. RANTES, MIP-1-alpha, IL-6, IL-8 and IL-10 were detected in NW and TA samples from all children with RSV infection. The concentrations of these cytokines in samples obtained from children with RSV infection were significantly greater than those in samples obtained from control children. NW WBC counts significantly correlated with NW RANTES, IL-6, IL-8 and IL-10 concentrations, whereas TA WBC counts significantly correlated with TA IL-6, IL-8, IL-10 and MIP-1-alpha concentrations. NW RSV concentrations correlated with NW WBC counts and with NW cytokine concentrations. Among children with RSV infection nonintubated patients had greater NW WBC counts and NW RANTES concentrations than intubated patients. TA RANTES, IL-8 and IL-10 concentrations inversely correlated with clinical markers of RSV disease severity. The presence of cytokines in NW and TA samples of children with RSV infection suggests that they have a role in mediating the respiratory tract inflammation induced by RSV. These observations could have implications for designing new therapeutic strategies directed at immunomodulation of RSV disease.