Increased Expression of the Glucocorticoid Receptor β in Infants With RSV Bronchiolitis

Abstract

The majority of studies on glucocorticoid treatment in respiratory syncytial virus (RSV) bronchiolitis concluded that there are no beneficial effects. We hypothesized that RSV-infected patients may have an increased glucocorticoid receptor (GR) β expression, the isoform that is unable to bind cortisol and exert an antiinflammatory action. By using real-time polymerase chain reaction, we studied the expression of α and β GR in the peripheral blood mononuclear cells obtained from 49 RSV-infected infants (<1 year of age) with severe (n = 29) and mild to moderate (n = 20) illness. In plasma, we analyzed the level of cortisol by radioimmunoassay and inflammatory cytokines interleukin (IL)-10, IL-6, tumor necrosis factor-α, IL-1β, IL-8, IL-12p70, IL-2, IL-4, IL-5, interferon-γ, and IL-17 by cytometric beads assay. Statistical analysis was performed by nonparametric analysis of variance. We found a significant increase of β GR expression in patients with severe illness compared with those with mild disease (P < .001) and with a group of healthy controls (P < .01). The α:β GR ratio decreased significantly in infants with severe disease compared with those with mild illness (P < .01) and with normal controls (P < .001). The expression of β GR was positively correlated with the clinical score of severity (r = .54; P < .0001). The decrease of the α:β GR ratio by an increase of β receptors expression is related to illness severity and may partly explain the insensitivity to corticoid treatment in RSV-infected infants. The increased expression of β GR could be a marker of disease severity.