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An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
Innate immune dysfunction is associated with enhanced disease severity in infants with severe respiratory syncytial
Cesar Mella1, M Carmen Suarez-Arrabal, Santiago Lopez
1Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, The Ohio State University School of Medicine, Columbus, OH 43205, USA.
Insights
Infants with severe respiratory syncytial virus (RSV) bronchiolitis show higher plasma cytokines but reduced immune cell production capacity. This immune dysregulation predicts worse outcomes, aiding in identifying at-risk infants.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Virology
Background:
- Most pediatric intensive care unit (PICU) admissions for respiratory syncytial virus (RSV) bronchiolitis occur in previously healthy infants.
- The relationship between immune markers and RSV disease severity is not fully understood.
Purpose of the Study:
- To investigate the association between serum cytokine concentrations, innate immune responsiveness, and the severity of RSV bronchiolitis in infants.
Main Methods:
- Blood samples were collected from infants with RSV bronchiolitis (PICU and floor admissions) and healthy controls.
- Plasma concentrations of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), IL-8, and IL-10 were measured.
- Whole blood lipopolysaccharide-stimulated cytokine production capacity was assessed.
Main Results:
- Plasma IL-6, IL-8, and IL-10 were higher in hospitalized infants than controls.
- Impaired TNF-α, IL-6, and IL-8 production capacity was observed in PICU patients compared to floor patients and controls.
- Decreased TNF-α and IL-8 production capacity correlated with longer hospital stays and increased disease severity scores.
Conclusions:
- Severe RSV bronchiolitis is characterized by elevated plasma cytokines and diminished innate immune cytokine production capacity.
- Immune monitoring may help identify infants at risk for severe RSV lower respiratory tract infection upon hospitalization.
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.
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