Immunological mechanisms of severe respiratory syncytial virus bronchiolitis

Abstract. Respiratory syncytial virus (RSV) bronchiolitis resulting in respiratory insufficiency is frequently encountered during the winter season in paediatric intensive care units. This review evaluates potential determinants described in severe RSV bronchiolitis with special attention to the role of immaturity of immune responses during infancy. Pre-existent cardiac or pulmonary compromises have been documented as clinical risk factors for severe RSV bronchiolitis. In addition to this group of infants with pre-morbidity, a large proportion of mechanically ventilated RSV bronchiolitis patients are previously healthy full-term infants or premature neonates without predisposing risk factors. In general, infants at this early age have maturation-related deficient cellular immunity. Several studies show an association between decreased cellular immunity and severe RSV bronchiolitis, indeed suggesting that a maturation-related defect of the cellular immune system facilitates severe RSV. In addition, low virus-specific antibody titres prior to RSV bronchiolitis have been shown to be a risk factor for severe RSV bronchiolitis. A low level of cellular and humoral immunity would explain that higher viral titres are found in infants with most severe illness. In conclusion, immaturity of the physiological functions in healthy pre-term infants and neonates, in particular the immune system, appears to be an important factor in the pathogenesis of RSV bronchiolitis resulting in mechanical ventilation.

[1]  L. Corey,et al.  Diminished interferon-gamma and lymphocyte proliferation in neonatal and postpartum primary herpes simplex virus infection. , 1992, The Journal of infectious diseases.

[2]  D. Sherrill,et al.  Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years , 1999, The Lancet.

[3]  R. Chanock,et al.  Influence of immunological factors in respiratory syncytial virus disease. , 1970, Archives of environmental health.

[4]  A. Eisen,et al.  The Relationship of Acute Bronchiolitis to Bronchial Asthma—A 4-to-14-year Follow-up , 1963, Pediatrics.

[5]  J. Sinnott,et al.  Respiratory Syncytial Virus , 1988, Infection Control & Hospital Epidemiology.

[6]  M. Adinolfi.  Ontogeny of human natural and acquired immunity. , 1997, Current topics in microbiology and immunology.

[7]  A. Milner,et al.  Analysis of cells obtained by bronchial lavage of infants with respiratory syncytial virus infection. , 1994, Archives of disease in childhood.

[8]  J. Lacroix,et al.  Respiratory failure and mechanical ventilation in severe bronchiolitis. , 1989, Archives of disease in childhood.

[9]  W. Dankner.  Reduction of Respiratory Syncytial Virus Hospitalization Among Premature Infants and Infants with Bronchopulmonary Dysplasia Using Respiratory Syncytial Virus Immune Globulin Prophylaxis , 1997, Pediatrics.

[10]  L. Bont,et al.  Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis. , 1999, The European respiratory journal.

[11]  C. Hall,et al.  Prophylactic Administration of Respiratory Syncytial Virus Immune Globulin to High-Risk Infants and Young Children , 1993 .

[12]  T. Noah,et al.  Respiratory syncytial virus-induced cytokine production by a human bronchial epithelial cell line. , 1993, The American journal of physiology.

[13]  G. Trinchieri,et al.  IL-12 as an adjuvant for cell-mediated immunity. , 1997, Seminars in immunology.

[14]  B. Graham,et al.  Pathogenesis of respiratory syncytial virus vaccine-augmented pathology. , 1995, American journal of respiratory and critical care medicine.

[15]  Christopher B Wilson,et al.  Immunity in the neonate , 1999 .

[16]  W. Morgan,et al.  Diminished lung function as a predisposing factor for wheezing respiratory illness in infants. , 1988, The New England journal of medicine.

[17]  A. Coutinho,et al.  Developmental shift in the patterns of interleukin production in early post‐natal life , 1994, European journal of immunology.

[18]  D. Shale,et al.  IL-8 and neutrophil elastase levels in the respiratory tract of infants with RSV bronchiolitis. , 1999, The European respiratory journal.

[19]  R. Holman,et al.  Bronchiolitis-associated hospitalizations among US children, 1980-1996. , 1999, JAMA.

[20]  W. Hicks,et al.  Respiratory syncytial virus and human bronchial epithelium. , 1998, Archives of otolaryngology--head & neck surgery.

[21]  R. M. Hendry,et al.  Antigenic characterization of respiratory syncytial virus strains with monoclonal antibodies. , 1985, The Journal of infectious diseases.

[22]  P. Openshaw.  Immunity and immunopathology to respiratory syncytial virus. The mouse model. , 1995, American journal of respiratory and critical care medicine.

[23]  D. W. Smith,et al.  Clinical observations on mechanical ventilation for respiratory failure in bronchiolitis , 1986, Pediatric pulmonology.

[24]  R. Douglas,et al.  Respiratory syncytial virus infections in infants: quantitation and duration of shedding. , 1976, The Journal of pediatrics.

[25]  M. Perkins,et al.  Primary respiratory syncytial virus infection in mice , 1988, Journal of medical virology.

[26]  W. Aherne,et al.  Pathological changes in virus infections of the lower respiratory tract in children , 1970, Journal of clinical pathology.

[27]  B. Adkins.  T-cell function in newborn mice and humans. , 1999, Immunology today.

[28]  L. Bont,et al.  Monocyte interleukin-12 production is inversely related to duration of respiratory failure in respiratory syncytial virus bronchiolitis. , 2000, The Journal of infectious diseases.

[29]  H. Friedman,et al.  Impaired cellular immunity to cytomegalovirus in congenitally infected children and their mothers. , 1979, The Journal of infectious diseases.

[30]  R. Douglas,et al.  Neonatal respiratory syncytial virus infection. , 1979, The New England journal of medicine.

[31]  B. Graham,et al.  Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice. , 1991, The Journal of clinical investigation.

[32]  R. Garofalo,et al.  Eosinophil degranulation in the respiratory tract during naturally acquired respiratory syncytial virus infection. , 1992, The Journal of pediatrics.

[33]  W. Maniscalco,et al.  Respiratory syncytial virus and premature infants born at 32 weeks' gestation or earlier: hospitalization and economic implications of prophylaxis. , 2000, Archives of pediatrics & adolescent medicine.

[34]  P. Renzi,et al.  Cellular immunity is activated and a TH-2 response is associated with early wheezing in infants after bronchiolitis. , 1997, The Journal of pediatrics.

[35]  Palivizumab, a Humanized Respiratory Syncytial Virus Monoclonal Antibody, Reduces Hospitalization From Respiratory Syncytial Virus Infection in High-risk Infants. , 1998, Pediatrics.

[36]  H. Wigzell,et al.  Regulation of immune functions in the fetus and newborn. , 1981, Progress in allergy.

[37]  R. Oates,et al.  Clinical severity of respiratory syncytial virus Group A and B infection in Sydney, Australia , 1993, The Pediatric infectious disease journal.

[38]  R. Chanock,et al.  An epidemiologic study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS virus vaccine. , 1969, American journal of epidemiology.

[39]  A. Sher,et al.  Mechanisms of innate resistance to Toxoplasma gondii infection. , 1997, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[40]  P. Gardner,et al.  Role of respiratory viruses in childhood mortality. , 1975, British medical journal.

[41]  S. Baron,et al.  Interleukin-1 alpha mediates the enhanced expression of intercellular adhesion molecule-1 in pulmonary epithelial cells infected with respiratory syncytial virus. , 1995, American journal of respiratory cell and molecular biology.

[42]  J. Johansen,et al.  Severity of respiratory syncytial virus disease related to type and genotype of virus and to cytokine values in nasopharyngeal secretions. , 1998, The Pediatric infectious disease journal.

[43]  C. Hall,et al.  Respiratory syncytial viral infection in infants with congenital heart disease. , 1982, The New England journal of medicine.

[44]  D. Wong,et al.  The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection. , 1981, The New England journal of medicine.

[45]  J. Kimpen,et al.  T cell subset analysis in peripheral blood of children with RSV bronchiolitis. , 1998, Scandinavian journal of infectious diseases.

[46]  C. Wilson,et al.  Immunologic basis for increased susceptibility of the neonate to infection. , 1986, The Journal of pediatrics.

[47]  Stephen T Holgate,et al.  Community study of role of viral infections in exacerbations of asthma in 9-11 year old children , 1995, BMJ.

[48]  P. Holt.  Postnatal maturation of immune competence during infancy and childhood , 1995, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[49]  R. Karron,et al.  Severe respiratory syncytial virus disease in Alaska native children. RSV Alaska Study Group. , 1999, The Journal of infectious diseases.

[50]  W. Calhoun,et al.  Respiratory syncytial virus infection in infants is associated with predominant Th-2-like response. , 1997, American journal of respiratory and critical care medicine.

[51]  E. Wang,et al.  Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) prospective study of risk factors and outcomes in patients hospitalized with respiratory syncytial viral lower respiratory tract infection. , 1995, The Journal of pediatrics.

[52]  Ö. Strannegård,et al.  Eosinophil cationic protein in nasopharyngeal secretions and serum of infants infected with respiratory syncytial virus , 1994, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[53]  E. Wang,et al.  Respiratory syncytial virus infection in pediatric patients , 1998 .

[54]  P. Ogra,et al.  The appearance of cell-bound IgE in respiratory-tract epithelium after respiratory-syncytial-virus infection. , 1980, The New England journal of medicine.

[55]  E. Yunis,et al.  Demonstration of respiratory syncytial virus in an autopsy series. , 1990, Pediatric pathology.

[56]  R. Crone,et al.  Management of respiratory failure in infants with acute viral bronchiolitis. , 1984, American journal of diseases of children.

[57]  L. Corey,et al.  Diminished Interferon-γ and Lymphocyte Proliferation in Neonatal and Postpartum Primary Herpes Simplex Virus Infection , 1992 .

[58]  C. Harman,et al.  Immunoglobulin and cytokine production by neonatal lymphocytes , 1991, Clinical and experimental immunology.

[59]  Testing models predicting severity of respiratory syncytial virus infection on the PICNIC RSV database. Pediatric Investigators Collaborative Network on Infections in Canada. , 1995, Archives of pediatrics & adolescent medicine.

[60]  L. Bont,et al.  Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity. , 2001, The Journal of infectious diseases.

[61]  E. Hey,et al.  Wheezing, asthma, and pulmonary dysfunction 10 years after infection with respiratory syncytial virus in infancy. , 1982, British medical journal.

[62]  A. Hayward,et al.  Herpes Simplex Virus-Stimulated γ-Interferon Production by Newborn Mononuclear Cells , 1986, Pediatric Research.

[63]  R. Jacobs,et al.  Immunobiology of childhood tuberculosis: a window on the ontogeny of cellular immunity. , 1997, The Journal of pediatrics.

[64]  Pk Smith,et al.  Leucocyte populations in respiratory syncytial virus‐induced bronchiolitis , 2001, Journal of paediatrics and child health.

[65]  M J Campbell,et al.  The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis. , 1996, American journal of respiratory and critical care medicine.

[66]  R. de Groot,et al.  Relationship between clinical severity of respiratory syncytial virus infection and subtype. , 1996, Archives of disease in childhood.

[67]  Cohen,et al.  Fetal natural killer cell function is suppressed , 1998, Immunology.

[68]  C. Mandl,et al.  Reduced interferon-gamma expression in peripheral blood mononuclear cells of infants with severe respiratory syncytial virus disease. , 1999, American journal of respiratory and critical care medicine.

[69]  L. Bont,et al.  Monocyte IL-10 production during respiratory syncytial virus bronchiolitis is associated with recurrent wheezing in a one-year follow-up study. , 2000, American journal of respiratory and critical care medicine.

[70]  H. Wigzell,et al.  Regulation of Immune Functions in the Fetus and Newborn1 , 1981 .