Skip to main content
Log in

Elevated cytokine levels in tracheobronchial aspirate fluids from ventilator treated neonates with bronchopulmonary dysplasia

  • Neonatology
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Abstract

Bronchopulmonary dysplasia (BPD) is a chronic lung disease often occurring in ventilator-treated very low birth weight infants. The aetiology of BPD is multifactorial and pulmonary immaturity, high oxygen concentrations, peak inspiratory pressure levels and large tidal volumes during prolonged mechanical ventilation are important factors. We measured in tracheobronchial aspirate fluid (TAF) the concentrations of the pro-inflammatory cytokines tumour necrosis factor α, interleukin-1β (IL-1β), IL-6, IL-8, and IL-1 receptor antagonist in infants requiring artificial ventilation for BPD (n=17) or respiratory distress syndrome (RDS) (n=15) or postoperatively after surgery (n=15). The median levels of all studied cytokines in TAF were higher in infants with BPD without local or systemic corticosteroid, treatment compared to the median TAF levels of BPD neonates treated with corticosteroids (P=0.06−P<0.01). The neonates with BPD not treated with corticosteroids also showed higher levels of the five studied cytokines in TAF compared to infants on short-time ventilator treatment (P<0.01−P<0.001) and compared to neonates with RDS (P=0.07−P<0.001). The corticosteroid treated neonates with BPD had TAF cytokine levels approaching those of the control neonates.

Conclusion

Tumour necrosis factors α, IL-1β, IL6, IL8 and IL 1 ra were markedly elevated in tracheobronchial aspirate fluids from neonates with bronchopulmonary dysplasia. Corticoid treatment seemed to reduce these levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

BPD :

bronchopulmonary dysplasia

IL-1 :

interleukin-1

IL-1ra :

interleukin-1 receptor antagonist

IL-6 :

interleukin-6

IL-8 :

interleukin-8

PMNL :

polymorphonuclear leucocytes

RDS :

respiratory distress syndrome

TAF :

tracheobronchial aspirate fluid

TNF :

tumour necrosis factor

References

  1. Arend WP (1991) Interleukin 1 receptor antagonist. A new member of the interleukin 1 family. J Clin Invest 88: 1445–1451

    Article  PubMed  CAS  Google Scholar 

  2. Bancalari E, Abdenour GE Feller R, Gannon J (1979) Bronchopulmonary dysplasia: clinical presentation. J Pediatr 95:819–823

    Article  PubMed  CAS  Google Scholar 

  3. Cassell GH, Crouse DT, Canupp KC, et al (1988) Association ofUreaplasma urealyticum infection of the lower respiratory tract with chronic lung disease and death, in very-low-birth-weight infants. Lancet II:240–245

    Article  Google Scholar 

  4. Clement A, Chadelat K, Sardet A, Grimfeld A, Tournier G (1988) Alveolar macrophage status in bronchopulmonary dysplasia. Pediatr Res 23: 470–473

    Article  PubMed  CAS  Google Scholar 

  5. Cummings JJ, D'Eugenio DB, Gross SJ (1989) A controlled trial of dexamethasone in preterm infants at high risk for bronchopulmonary dysplasia. N Engl J Med 320.:1505–1510

    PubMed  CAS  Google Scholar 

  6. D'Ablang G, Bernard B, Zaharov I, Barton L, Kaplan B, Schwinn CP (1975) Neonatal pulmonary cytology and bronchopulmonary dysplasia. Acta Cytol 19:21–27

    PubMed  Google Scholar 

  7. Dinarello CA (1991) The proinflammatory cytokines interleukin-1 and tumor necrosis factor and treatment of the septic shock syndrome. J. Infect Dis 163:1177–1184

    PubMed  CAS  Google Scholar 

  8. Dinarello CA, Wolff SM (1993) The role of interleukin-1 in disease. N Engl J Med 328:106–113

    Article  PubMed  CAS  Google Scholar 

  9. Donnelly SC, Strieter RM, Kunkel SL, et al (1993) Interleukin-8 and development of respiratory distress syndrome in at-risk patient groups. Lancet 341: 643–647

    Article  PubMed  CAS  Google Scholar 

  10. Gerdes JS, Harris MC, Polin RA (1988) Effects of dexamethasone and indomethacin on elastase, α2-proteinase inhibitor, and fibronectin in bronchoalveolar lavage fluid from neonates. J Pediatr 113:727–773

    Article  PubMed  CAS  Google Scholar 

  11. Giedion A, Haefliger H, Dangel P (1973) Acute pulmonary X-ray changes in hyaline membrane disease treated with artificial ventilation and positive end-expiratory pressure (PEEP). Pediatr Radiol 1:145–152

    Article  PubMed  CAS  Google Scholar 

  12. Grigg JM, Barber A, Silverman M (1991) Increased levels of bronchoalveolar lavage fluid interleukin-6 in preterm ventilated infants after prolonged rupture of membranes. Am Rev Respir Dis 145:782–786

    Google Scholar 

  13. Groneck P, Speer CP (1993) Interleukin-8 in pulmonary efflnent fluid of preterm infants. J Pediatr 123:839–840

    PubMed  CAS  Google Scholar 

  14. Jorens PG, Richmaneisenstat JBY, Housset BP, et al (1992) Interleukin-8 induces neutrophil accumulation but not protease secretion in the canine trachea. Am J Physiol 6:L708–713

    Google Scholar 

  15. Knowles MR, Church NL, Waltner WE, et al (1990) A pilot study of aerolized amiloride for the treatment of lung disease in cystic fibrosis. N Engl J Med 322:1189–1194

    PubMed  CAS  Google Scholar 

  16. LaForce WR, Brudno DS (1993) Controlled trial of beclomethasone dipropionate by nebulization in oxygen- and ventilator-dependent infants. J Pediatr 122:285–288

    Article  PubMed  CAS  Google Scholar 

  17. Mammel MC, Johnson DE., Green TP, Thompson TR (1983) Controlled trial of dexamethasone therapy in infants with bronchopulmonary dysplasia. Lancet I:1356–1358

    Article  Google Scholar 

  18. McColm JR, McIntosh N (1994) Interleukin-8 in bronchoalveolar lavage samples as a predictor of chronic lung disease in premature infants. Lancet 343:729

    Article  PubMed  CAS  Google Scholar 

  19. Merritt TA, Stuard ID, Puccia J, et al (1981) Newborn tracheal aspirate cytology: Classification during respiratory distress syndrome and bronchopulmonary dysplasia. J Pediatr 98: 949–956

    Article  PubMed  CAS  Google Scholar 

  20. Merritt TA, Puccia JM, Stuard ID (1981) Cytologic evaluation of pulmonary effluent in neonates with respiratory distress syndrome and bronchopulmonary dysplasia. Acta Cytol 25: 631–639

    PubMed  CAS  Google Scholar 

  21. Merritt TA, Cochrane CG, Holcomb K, et al (1983) Elastase and α2-proteinase inhibitor activity in tracheal aspirates during respiratory distress syndrome. J Clin Invest 72:656–666

    Article  PubMed  CAS  Google Scholar 

  22. Millar AB, Singer M, Meager A, Foley NM, Johnson NMcI, Rook GAW (1989) Tumour necrosis factor in bronchopulmonary secretions of patients with adult respiratory distress syndrome. Lancet II:712–714

    Article  Google Scholar 

  23. Miller EJ, Cohen AB, Nagao S, et al (1992) Elevated levels of NAP-1/interleukin-8 are present in the airspaces of patients with the adult respiratory distress syndrome and are associated with increased mortality. Am Rev Respir Dis 146:427–432

    PubMed  CAS  Google Scholar 

  24. Murch SH, MacDonald TT, Wood CBS, Costeloe KL (1992) Tumour necrosis factor in the bronchoalveolar secretions of infants with the respiratory distress syndrome and the effect of dexamethasone treatment. Thorax 47: 44–47

    Article  PubMed  CAS  Google Scholar 

  25. Ng PC (1993) The effectiveness and side effects of dexamethasone in preterm infants with bronchopulmonary dysplasia. Arch Dis Child 68: 330–336

    Article  PubMed  CAS  Google Scholar 

  26. Noack G, Mortensson W, Robertson B, Nilsson R (1993) Correlations between radiological and cytological findings in early development of bronchopulmonary dysplasia. Eur J Pediatr 152: 1024–1029

    Article  PubMed  CAS  Google Scholar 

  27. Northway WH (1990) Bronchopulmonary dysplasia: then and now. Arch Dis Child 65:1076–1081

    Article  PubMed  Google Scholar 

  28. Northway WH, Rosan RC, Porte DY (1967) Pulmonary disease following respirator therapy of hyaline-membrane disease. N. Engl J Med 276:357–368

    PubMed  Google Scholar 

  29. Ohlsson K, Björk P, Bergenfeldt M, Hageman R Thompson RC (1990) Interleukin-1 receptor antagonist reduces mortality from endotoxin shock. Nature 348:550–552

    Article  PubMed  CAS  Google Scholar 

  30. Philip AGS (1975) Oxygen plus pressure plus time: the etiology of bronchopulmonary dysplasia. Pediatrics 55: 44–50

    PubMed  CAS  Google Scholar 

  31. Rolfe MW, Kunkel SL, Rowens B, Standiford TJ, Cragoe EJ, Strieter RM (1992) Suppression of human alveolar macrophage-derived cytokines by amiloride. Am J Respir Cell Mol Biol 6:576–582

    PubMed  CAS  Google Scholar 

  32. Rosenfeld W, Evans H, Concepcion L, Jhaveri R, Schaeffer H, Friedman A (1984) Prevention of bronchopulmonary dysplasia by administration of bovine superoxide dismutase in preterm infants with respiratory distress syndrome. J Pediatr 105:781–788

    Article  PubMed  CAS  Google Scholar 

  33. Schröder JM (1992) Interleukin 8. Advances Neuroimmunol 2: 109–124

    Article  Google Scholar 

  34. Snick van J (1990) Interleukin-6: an overview. Annu Rev Immunol 8:253–278

    Article  PubMed  Google Scholar 

  35. Southall DP, Samuels MP (1990) Bronchopulmonary dysplasia: a new look at management. Arch Dis Child 65:1089–1095

    Article  PubMed  CAS  Google Scholar 

  36. Suter PM, Suter S, Girardin E, Roux-Lombard P, Grau GE, Dayer J-M (1992) High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. Am Rev Respir Dis 145:1016–1022

    PubMed  CAS  Google Scholar 

  37. Svenningsen NW (1984) Clinical criteria of RDS. In: Raivio KO, Hallman N, Kouvalainen K (eds) Respiratory distress syndrome. Academic Press, London, pp 133–145

    Google Scholar 

  38. Wakabayashi G, Gelfand JA, Burke JF, Thompson RC, Dinarello CA (1991) A specific receptor antagonist for interleukin 1 preventsEscherichia coli-induced shock in rabbits. FASEB J 5: 338–343

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tullus, K., Noack, G.W., Burman, L.G. et al. Elevated cytokine levels in tracheobronchial aspirate fluids from ventilator treated neonates with bronchopulmonary dysplasia. Eur J Pediatr 155, 112–116 (1996). https://doi.org/10.1007/BF02075762

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02075762

Key words

Navigation