Nasopharyngeal aspirate cytokine levels 1 yr after severe respiratory syncytial virus infection

Abstract

Respiratory syncytial virus (RSV) infection is an important cause of recurrent wheezing in infants. Nevertheless, the link between RSV infection and wheezing has yet to be elucidated at the molecular level. Here, we present a preliminary study on the evolution of the immune response in the respiratory tract at long-term after RSV infection. Twenty-seven immune mediators were profiled in nasopharyngeal aspirates (NPAs) obtained from 20 children hospitalized due to a severe infection by RSV at discharge from hospital and again 1 yr later. The same mediators were profiled in parallel in NPAs from 12 healthy controls. In the year following discharge, 85% (17/20) of children of the RSV group suffered at least one episode of wheezing documented by the pediatrician. On the contrary, wheezing episodes were observed only in 25% (3/12) of children in the control group. While most of the mediators profiled returned to normal levels by 1 yr after discharge from hospital, RSV children showed a persistent nasal hyper-secretion of VEGF, G-CSF, IL-10, IL-6, IFN-gamma, IL-7 and IL-13. In previous works VEGF, IL-10 and IFN-gamma have been put in relation with the pathogenesis of post-virus induced asthma. G-CSF, IL-6, IL-7 and IL-13 are increased in respiratory and plasma samples of asthmatic patients. Here, we evidence for the first time a persistent elevation of these mediators as late as 1 yr after severe RSV disease resolution, reinforcing their possible implication in the pathogenesis of wheezing.

Airway IFN-γ Production During RSV Bronchiolitis is Associated with Eosinophilic Inflammation

“…Respiratory viral infection alone was insufficient to induce increased levels of these Th2 cytokines. The below-sensitivity findings of IL-5 and IL-13 in our control group were also mirrored in a study by Pino et al [21]. The timing of cytokine measurements should also be mentioned, as it has been demonstrated that acute-and convalescent-phase cytokine profiles in RSV patients may differ.…”

Cytokine responses in primary and secondary respiratory syncytial virus infections

“…In contrast, Bermejo-Martin et al (22) found lower levels of IL-17 in nasal secretions of infants with RSV bronchiolitis at discharge as compared to admission. The same group also found IL-17 levels in nasal samples taken 1 year after an admission with RSV bronchiolitis were elevated compared with controls (23).…”

“…IL-17-producing T cells are induced in primary infections through pathways that involve STAT3 and IL-6 (16,17). High levels of IL-6 have been found in the airways of infants with RSV bronchiolitis (18,19), and a number of studies have identified IL-17 in the airways (20)(21)(22)(23)(24) and plasma (21,24) of infants with RSV infection. Two studies have found lower levels of IL-17 in the airways of the most severely affected infants, and the authors suggested that higher IL-17 levels were associated with protection against more severe disease (21,24).…”

Differential cytopathogenesis of respiratory syncytial virus prototypic and clinical isolates in primary pediatric bronchial epithelial cells

“…These data contrast with previous reports in which RSV infection of monolayers resulted in increased IL-6 expression [13,14,33], while work by Bem et al suggested that TRAIL might contribute to lung epithelial injury in children with severe RSV infection [17]. Like TRAIL, VEGF is a cytokine associated with RSV or rhinovirus infection in airway bronchial cells grown in monolayer [36] and has been detected in nasopharyngeal aspirates from children hospitalized with severe RSV infection [37]. However, unlike TRAIL and IL-6, in our model, VEGF was secreted at similar levels in both infected and uninfected PBEC cultures.…”