title: Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis.
abstract: The role of cellular immunity in disease severity in respiratory syncytial virus (RSV) bronchiolitis is largely unknown. This study investigated the association between disease severity and systemic cytokine responses in hospitalized ventilated and nonventilated RSV bronchiolitis patients. In whole blood cultures stimulated with phytohaemagglutinin (PHA), lymphoproliferative responses and interferon (IFN)-gamma and interleukin (IL)-4 production during acute illness were measured. In addition, plasma cytokines were measured. Measurements were repeated in the convalescent phase, 3-4 weeks after admission. Fifty patients were included. The median age in ventilaled patients was significantly lower than in nonventilated patients (1 versus 4 months, p<0.05). In comparison with nonventilated patients, the ventilated patients had significantly lower lymphoproliferative responses and a lower production of IFN-gamma and IL-4. In fact, IFN-gamma and IL-4 production in ventilated patients was almost completely undetectable. Plasma IL-8 levels in ventilated patients were significantly higher than in nonventilated patients. In the convalescent phase, lymphoproliferative and cytokine responses as well as plasma IL-8 levels were normal in both patient groups. Since RSV bronchiolitis is associated with the subsequent development of asthma, the possible skewing of the T-helper (Th1/Th2) cytokine balance was investigated. This was found neither in the acute nor in the convalescent phase. In conclusion, the data indicate that depressed lymphocyte function and elevated plasma interleukin-8 levels are markers of severe disease. It is suggested that age and maturation related immune mechanisms could explain the occurrence of severe respiratory syncytial virus bronchiolitis requiring mechanical ventilation in young infants.
authors.affiliation: University Hospital for Children and Youth Het Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Bont
authors.forename: C J
authors.initials: CJ
authors.lastname: Heijnen
authors.forename: A
authors.initials: A
authors.lastname: Kavelaars
authors.forename: W M
authors.initials: WM
authors.lastname: van Aalderen
authors.forename: F
authors.initials: F
authors.lastname: Brus
authors.forename: J T
authors.initials: JT
authors.lastname: Draaisma
authors.forename: S M
authors.initials: SM
authors.lastname: Geelen
authors.forename: H J
authors.initials: HJ
authors.lastname: van Vught
authors.forename: J L
authors.initials: JL
authors.lastname: Kimpen
mesh_terms: D000914:Antibodies, Viral / Q000032:analysis; D015415:Biomarkers / Q000097:blood; D001990:Bronchiolitis, Viral / Q000097:blood* / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000097:blood*; D018664:Interleukin-12 / Q000097:blood*; D015847:Interleukin-4 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D010835:Phytohemagglutinins; D018357:Respiratory Syncytial Virus Infections / Q000097:blood* / Q000276:immunology / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000276:immunology / Q000302:isolation & purification; D012720:Severity of Illness Index; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D016209:Interleukin-8; D010835:Phytohemagglutinins; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma