Innate immune dysfunction is associated with enhanced disease severity in infants with severe respiratory syncytial virus bronchiolitis

Abstract

Background: Most patients with respiratory syncytial virus (RSV) bronchiolitis requiring admission to the pediatric intensive care unit (PICU) have no risk factors for severe disease. We sought to investigate the relationship between serum cytokine concentrations, innate immune responsiveness, and RSV disease severity.

Methods: Previously healthy infants (median age, 2.6 months) with RSV bronchiolitis (PICU, n = 20; floor, n = 46) and healthy matched controls (n = 14) were enrolled, and blood samples were obtained within 24 hours of admission to measure plasma tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) concentrations and, whole blood lipopolysaccharide-stimulated cytokine production capacity.

Results: Plasma IL-6, IL-8, and IL-10 concentrations were comparable between PICU and floor patients, but higher than in healthy controls (P < .05). In contrast, TNF-α, IL-6, and IL-8 production capacity was significantly decreased in PICU compared with both floor patients and healthy controls. In adjusted analyses, only impaired TNF-α and IL-8 production capacity were associated with longer length of stay (P = .035) and greater disease severity scores (P = .001).

Conclusions: Infants with severe RSV bronchiolitis had increased plasma cytokine concentrations and yet impaired innate immunity cytokine production capacity, which predicted worse disease outcomes. Immune monitoring of otherwise healthy infants with RSV lower respiratory tract infection could help identify patients at risk for severe disease at the time of hospitalization.

Figure 1.

Lipopolysaccharide-stimulated cytokine concentrations in whole blood. Horizontal lines represent median values; top and bottom whiskers, 10th and 90th percentile values, respectively, for each group. P values were determined with the Mann–Whitney rank sum test. Abbreviations: IL-6, interleukin 6; IL-8, interleukin 8; IL-10, interleukin 10; NS, not statistically significant; PICU, pediatric intensive care unit; TNF-α, tumor necrosis factor α.

Figure 2.

Ex vivo tumor necrosis factor α production grouped by total hospital length of stay in all patients (A) and those hospitalized in the pediatric intensive care unit (B). *Statistically significant by Mann–Whitney rank sum test compared with production in patients with a length of stay 1–2 (A) or 3–6 (B) days. P < .05. Abbreviations: PICU, pediatric intensive care unit; TNF-α, tumor necrosis factor α.