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Airway IFN-γ Production During RSV Bronchiolitis is Associated with Eosinophilic Inflammation

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Abstract

Study Objective

This study was designed to investigate the possible role of IFN-γ in eosinophil degranulation that occurs during respiratory syncytial virus (RSV) bronchiolitis.

Methods

Sixty-seven infants, 2–24 months old and hospitalized with their first episode of acute RSV bronchiolitis, were selected for this study. Eosinophil-active cytokine and chemokine profiles in nasal lavage supernatants taken within the first 48 h of admission were determined by a multiplex bead array system (Luminex). Comparisons were made with control (Control group) subjects (n = 20).

Results

Nasal IFN-γ levels were significantly higher (P < 0.0001) in RSV bronchiolitis (median = 4.4 pg/ml) infants compared to controls (0.0 pg/ml). IFN-γ levels correlated significantly with the levels of nasal eotaxin (r = 0.566, P < 0.0001), RANTES (r = 0.627, P < 0.0001), GM-CSF (r = 0.849, P < 0.0001), and EDN (r = 0.693, P < 0.001). Nasal interleukin (IL)-4, IL-5, and IL-13 were below sensitivity levels in most RSV bronchiolitis and control subjects.

Conclusion

These results suggest that IFN-γ may play an important role in eosinophilic inflammation in RSV bronchiolitis.

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References

  1. Welliver JR, Welliver RC (1993) Bronchiolitis. Pediatr Rev 14:134–139

    Article  PubMed  CAS  Google Scholar 

  2. Sigurs N, Gustafsson PM, Bjarnason R, Lundberg F, Schmidt S, Sigurbergsson F et al (2005) Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med 171:137–141

    Article  PubMed  Google Scholar 

  3. Welliver RC, Wong DT, Sun M, Middleton E Jr, Vaughan RS, Ogra PL (1981) The development of respiratory syncytial virus-specific IgE and the release of histamine in nasopharyngeal secretions after infection. N Engl J Med 305:841–846

    Article  PubMed  CAS  Google Scholar 

  4. Harrison AM, Bonville CA, Rosenberg HF, Domachowske JB (1999) Respiratory syncytical virus-induced chemokine expression in the lower airways: eosinophil recruitment and degranulation. Am J Respir Crit Care Med 159:1918–1924

    PubMed  CAS  Google Scholar 

  5. Wang SZ, Smith PK, Lovejoy M, Bowden JJ, Alpers JH, Forsyth KD (1998) Shedding of L-selectin and PECAM-1 and upregulation of Mac-1 and ICAM-1 on neutrophils in RSV bronchiolitis. Am J Physiol 275:L983–L989

    PubMed  CAS  Google Scholar 

  6. Robinson DS, Durham SR, Kay AB (1993) Cytokines in asthma. Thorax 48:845–853

    Article  PubMed  CAS  Google Scholar 

  7. van Schaik SM, Tristram DA, Nagpal IS, Hintz KM, Welliver RC 2nd, Welliver RC (1999) Increased production of IFN-γ and cysteinyl leukotrienes in virus-induced wheezing. J Allergy Clin Immunol 103:630–636

    Article  PubMed  Google Scholar 

  8. Schwarze J, Hamelmann E, Bradley KL, Takeda K, Gelfand EW (1997) Respiratory syncytial virus infection results in airway hyperresponsiveness and enhanced airway sensitization to allergen. J Clin Invest 100:226–233

    Article  PubMed  CAS  Google Scholar 

  9. van Schaik SM, Obot N, Enhorning G, Hintz K, Gross K, Hancock GE et al (2000) Role of interferon gamma in the pathogenesis of primary respiratory syncytial virus infection in BALB/c mice. J Med Virol 62:257–266

    Article  PubMed  Google Scholar 

  10. Gleich GJ, Adolphson CR, Kita H (2000) The eosinophil and asthma. In: Busse WW, Holgate ST (eds) Asthma and rhinitis, vol. 1, 2nd edn. Blackwell, Oxford, pp 429–479

    Google Scholar 

  11. Collins PD, Marleau S, Griffiths-Johnson DA, Jose PJ, Williams TJ (1995) Cooperation between interleukin-5 and the chemokine eotaxin to induce eosinophil accumulation in vivo. J Exp Med 182:1169–1174

    Article  PubMed  CAS  Google Scholar 

  12. Everard ML (1996) Acute bronchiolitis—a perennial problem [letter]. Lancet 348:279–280

    Article  PubMed  CAS  Google Scholar 

  13. Parkin PC, Macarthur C, Saunders NR, Diamond SA, Winders PM (1996) Development of a clinical asthma score for use in hospitalized children between 1 and 5 years of age. J Clin Epidemiol 49:821–825

    Article  PubMed  CAS  Google Scholar 

  14. Kaul A, Scott R, Gallagher M, Scott M, Clement J, Ogra PL (1978) Respiratory syncytial virus infection: rapid diagnosis in children by use of indirect immunofluorescence. Am J Dis Child 132:1088–1090

    PubMed  CAS  Google Scholar 

  15. Brenton S (1997) RSV specimen collection methods: nasal vs. nasopharyngeal. Pediatr Nurs 23:621–622

    Google Scholar 

  16. Kidd P (2003) Th1/Th2 balance: the hypothesis, its limitations, and implications for health and disease. Altern Med Rev 8:223–246

    PubMed  Google Scholar 

  17. Kim CK, Kim SW, Park CS, Kim BI, Kang H, Koh YY (2003) Bronchoalveolar lavage cytokine profiles in acute asthma and acute bronchiolitis. J Allergy Clin Immunol 112:64–71

    Article  PubMed  CAS  Google Scholar 

  18. Chen ZM, Mao JH, Du LZ, Tang YM (2002) Association of cytokine responses with disease severity in infants with respiratory syncytial virus infection. Acta Paediatr 91:914–922

    Article  PubMed  CAS  Google Scholar 

  19. Bennett BL, Garofalo RP, Cron SG, Hosakote YM, Atmar RL, Macias CG et al (2007) Immunopathogenesis of respiratory syncytial virus bronchiolitis. J Infect Dis 195:1532–1540

    Article  PubMed  CAS  Google Scholar 

  20. Siegle JS, Hansbro N, Herbert C, Rosenberg HF, Domachowske JB, Asquith KL et al (2010) Early-life viral infection and allergen exposure interact to induce an asthmatic phenotype in mice. Respir Res 11:14

    Article  PubMed  Google Scholar 

  21. Pino M, Kelvin DJ, Bermejo-Martin JF, Alonso A, Matias V, Tenorio A et al (2009) Nasopharyngeal aspirate cytokine levels 1 yr after severe respiratory syncytial virus infection. Pediatr Allergy Immunol 20:791–795

    Article  PubMed  Google Scholar 

  22. Jartti T, Paul-Anttila M, Lehtinen P, Parikka V, Vuorinen T, Simell O et al (2009) Systemic T-helper and T-regulatory cell type cytokine responses in rhinovirus vs. respiratory syncytial virus induced early wheezing: an observational study. Respir Res 10:85

    Article  PubMed  Google Scholar 

  23. Salvi SS, Babu KS, Holgate ST (2001) Is asthma really due to a polarized T cell response toward a helper T cell type 2 phenotype? Am J Respir Crit Care Med 164:1343–1346

    PubMed  CAS  Google Scholar 

  24. Valerius T, Repp R, Kalden JR, Platzer E (1990) Effects of IFN on human eosinophils in comparison with other cytokines. A novel class of eosinophil activators with delayed onset of action. J Immunol 145:2950–2958

    PubMed  CAS  Google Scholar 

  25. Yamaguchi T, Kimura H, Kurabayashi M, Kozawa K, Kato M (2008) Interferon-gamma enhances human eosinophil effector functions induced by granulocyte-macrophage colony-stimulating factor or interleukin-5. Immunol Lett 118:88–95

    Article  PubMed  CAS  Google Scholar 

  26. Simon HU (2008) Regulation of cell survival. In: Adkinson NF Jr, Bochner BS, Busse WW, Holgate ST, Lemanske RF Jr, Simons FER (eds) Adkinson: middleton’s allergy: principles and practice, 7th ed. Mosby, St. Louis, pp 413–422

    Google Scholar 

  27. Lacy P, Mahmudi-Azer S, Bablitz B, Hagen SC, Velazquez JR, Man SF et al (1999) Rapid mobilization of intracellularly stored RANTES in response to interferon-gamma in human eosinophils. Blood 94:23–32

    PubMed  CAS  Google Scholar 

  28. Matsukura S, Kokubu F, Kuga H, Kawaguchi M, Ieki K, Odaka M et al (2003) Differential regulation of eotaxin expression by IFN-gamma in airway epithelial cells. J Allergy Clin Immunol 111:1337–1344

    Article  PubMed  CAS  Google Scholar 

  29. Czech W, Krutmann J, Budnik A, Schopf E, Kapp A (1993) Induction of intercellular adhesion molecule 1 (ICAM-1) expression in normal human eosinophils by inflammatory cytokines. J Invest Dermatol 100:417–423

    Article  PubMed  CAS  Google Scholar 

  30. Zhenying N, Nelson CS, Jacoby DB, Fryer AD (2007) Expression and regulation of intercellular adhesion molecule-1 on airway parasympathetic nerves. J Allergy Clin Immunol 119:1415–1422

    Article  Google Scholar 

  31. Stark JM, Godding V, Sedgwick JB, Busse WW (1996) Respiratory syncytial virus infection enhances neutrophil and eosinophil adhesion to cultured respiratory epithelial cells. J Immunol 156:4774–4782

    PubMed  CAS  Google Scholar 

  32. Ishihara C, Ochiai K, Kagami M, Takashahi H, Matsuyama G, Yoshida S et al (1997) Human peripheral eosinophils express functional interferon-gamma receptors (IFN-gammaR). Clin Exp Immunol 110:524–529

    Article  PubMed  CAS  Google Scholar 

  33. Brandenburg AH, Kleinjan A, van Het Land B, Moll HA, Timmerman HH, de Swart RL et al (2000) Type 1-like immune response is found in children with Resiratory Syncytial Virus infection regardless of clinical severity. J Med Virol 62:267–277

    Article  PubMed  CAS  Google Scholar 

  34. Busse WW (1998) Inflammation in asthma: the cornerstone of the disease and target of therapy. J Allergy Clin Immunol 102:S17–S22

    Article  PubMed  CAS  Google Scholar 

  35. Grossman J (1997) One airway, one disease. Chest 111:11S–16S

    Article  PubMed  CAS  Google Scholar 

  36. Ciprandi G, Cirillo I (2006) The lower airway pathology of rhinitis. J Allergy Clin Immunol 118:1105–1109

    Article  PubMed  Google Scholar 

  37. Pitrez PM, Brennan S, Turner S, Sly PD (2005) Nasal wash as an alternative to bronchoalveolar lavage in detecting early pulmonary inflammation in children with cystic fibrosis. Respirology 10:177–182

    Article  PubMed  CAS  Google Scholar 

  38. Bont L, Heijnen CJ, Kavelaars A, van Aalderen WM, Brus F, Draaisma JM et al (2001) Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity. J Infect Dis 184:355–358

    Article  PubMed  CAS  Google Scholar 

  39. Hall CB, Douglas RG Jr, Geiman JM (1976) Respiratory syncytial virus infections in infants: quantitation and duration of shedding. J Pediatr 89:11–15

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Yuhan Corporation for their generous provision of cytokine kits. This study was supported in part by a 2011 Inje University Research Grant.

Conflict of interest

The authors state that they have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Pediatrics, Asthma and Allergy Center, Inje University Sanggye Paik Hospital, Seoul, Korea

    Chang Keun Kim, Zak Callaway & Soo-Hee Kim

  2. School of Biological Sciences, College of Natural Science, University of Ulsan, Ulsan, Korea

    Zak Callaway

  3. Department of Pediatrics, Seoul National University Hospital, Seoul, Korea

    Young Yull Koh

  4. Institute for Clinical Research, Mie National Hospital, 357 Osato-kubota, Tsu, Mie, 514-0124, Japan

    Takao Fujisawa

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  1. Chang Keun Kim
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  2. Zak Callaway
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  5. Takao Fujisawa
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Correspondence to Takao Fujisawa.

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Kim, C.K., Callaway, Z., Koh, Y.Y. et al. Airway IFN-γ Production During RSV Bronchiolitis is Associated with Eosinophilic Inflammation. Lung 190, 183–188 (2012). https://doi.org/10.1007/s00408-011-9349-5

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  • DOI: https://doi.org/10.1007/s00408-011-9349-5

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