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Intensive Care Medicine

, Volume 31, Issue 2, pp 272–280 | Cite as

Topical interleukin-8 antibody attracts leukocytes in a piglet lavage model

  • Tobias Ankermann
  • Tina Wiemann
  • Anja Reisner
  • Marzenna Orlowska-Volk
  • Heike Köhler
  • Martin F. KrauseEmail author
Experimental

Abstract

Objective

Acute respiratory distress syndrome (ARDS) in young infants is linked with a pulmonary inflammatory response part of which are increased interleukin-8 (IL-8) levels and migration of polymorphonuclear leukocytes (PMNL) into lung tissue. A topical application of an antibody against IL-8 might therefore decrease PMNL migration and improve lung function.

Design

Randomized, controlled, prospective animal study.

Setting

Research laboratory of a university children’s hospital.

Subjects and interventions

Anesthetized, mechanically ventilated newborn piglets (n=22) underwent repeated airway lavage to remove surfactant and to induce lung inflammation. Piglets then received either surfactant alone (S, n=8), or a topical antibody against IL-8 admixed to surfactant (S+IL-8, n=8), or an air bolus injection (control, n=6).

Measurements and results

After 6 h of mechanical ventilation following intervention, oxygenation [S 169±51 (SD) vs S+IL-8 139±61 mmHg] and lung function (compliance: S 1.3±0.4 vs S+IL-8 0.9±0.4 ml/cmH2O/kg; extra-vascular lung-water: S 27±9 vs S+IL-8 52±28 ml/kg) were worse in the S+IL-8 group because reactive IL-8 production [S 810 (median, range 447–2323] vs S+IL-8 3485 (628–16180) pg/ml; P<0.05) with facilitated migration of PMNL into lung tissue occurred. Moreover, antibody application caused augmented chemotactic potency of IL-8 [linear regression of migrated PMNL and IL-8 levels: S r 2 =0.30 (P=ns) vs S+IL-8 r 2 =0.89 (P=0.0002)].

Conclusion

Topical anti-IL-8 treatment after lung injury increases IL-8 production, PMNL migration, and worsens lung function in our piglet lavage model. This effect is in contrast to current literature using pre-lung injury treatment protocols. Our data do not support anti-IL-8 treatment in young infants with ARDS.

Keywords

Interleukin-8 antibody Airway lavage Lung function Migration Polymorphonuclear leukocytes Inflammation 

Notes

Acknowledgments

The surfactant preparation used in this study (Curosurf) was generously provided by Nycomed, Unterschleissheim, Germany. The authors are indebted to Jürgen Schulte-Mönting for statistical advice.

References

  1. 1.
    Lotze A, Mitchell BR, Bulas DI, Zola EM, Shalwitz RA, Gunkel JH, and the Survanta in Term Infants Group (1998) Multicenter study of surfactant (beractant) use in the treatment of term infants with severe respiratory failure. J Pediatr 132:40–47PubMedGoogle Scholar
  2. 2.
    LeVine AM, Lotze A, Stanley S, Stroud C, O’Donnell R, Whitsett J, Pollack MM (1996) Surfactant content in children with inflammatory lung disease. Crit Care Med 24:1062–1067CrossRefPubMedGoogle Scholar
  3. 3.
    Marraro GA, Luchetti M, Galassini EM, Abbiati G (1999) Natural surfactant supplementation in ARDS in pediatric age. Minerva Anestesiol 65:92–97PubMedGoogle Scholar
  4. 4.
    Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R (1994) The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 149:818–824PubMedGoogle Scholar
  5. 5.
    Anderson MR (2003) Update on pediatric respiratory distress syndrome. Respir Care 48:261–276PubMedGoogle Scholar
  6. 6.
    Rossi AG, Haslett C (1998) Inflammation, cell injury, and apoptosis. In: Said SI (ed) Proinflammatory and antiinflammatory peptides. Lung biology in health and disease. Marcel Dekker, New York, pp 9–24Google Scholar
  7. 7.
    Ware LB, Matthay MA (2000) The acute respiratory distress syndrome. N Engl J Med 342:1334–1349CrossRefPubMedGoogle Scholar
  8. 8.
    Vaddi K, Keller M, Newton RC (1997) The chemokine factsbook. Academic Harcourt Brace, San Diego, pp 23–37Google Scholar
  9. 9.
    Meduri GU, Headley S, Kohler G, Stentz F, Tolley E, Umberger R, Leeper K (1995) Persistent elevation of inflammatory cytokines predicts a poor outcome in ARDS. Plasma IL-1beta and IL-6 levels are consistent and efficient predictors of outcome over time. Chest 107:1062–1073PubMedGoogle Scholar
  10. 10.
    Meduri GU, Kohler G, Headley S, Tolley E, Streutz F, Postlethwaite A (1995) Inflammatory cytokines in the BAL of patients with ARDS; persistent elevation over time predicts poor outcome. Chest 108:1303–1314PubMedGoogle Scholar
  11. 11.
    Kurdowska A, Miller EJ, Noble JM, Baughman RP, Matthay MA, Brelsford WG, Cohen AB (1996) Anti-IL-8 autoantibody in alveolar fluid from patients with the adult respiratory distress syndrome. J Immunol 157:2699–2706PubMedGoogle Scholar
  12. 12.
    Sekido N, Mukaida N, Harada A, Nakanishi I, Watanabe Y, Matsushima K (1993) Prevention of lung reperfusion injury in rabbits by a monoclonal antibody against interleukin-8. Nature 365:654–657CrossRefPubMedGoogle Scholar
  13. 13.
    Mulligan MS, Jones ML, Bolanowski MA, Baganoff MP, Deppeler CL, Meyers DM, Ryan US, Ward PA (1993) Inhibition of lung inflammatory reactions in rats by an anti-human IL-8 antibody. J Immunol 150:5585–5595PubMedGoogle Scholar
  14. 14.
    Folkesson HG, Matthay MA, Hebert C, Broaddus VC (1995) Acid aspiration-induced lung injury in rabbits is mediated by IL-8 dependent mechanisms. J Clin Invest 96:107–116PubMedGoogle Scholar
  15. 15.
    Yokoi K, Mukaida N, Harada A, Watanabe Y, Matsushima K (1997) Prevention of endotoxemia-induced acute respiratory distress syndrome-like lung injury in rabbits by a monoclonal antibody to IL-8. Lab Invest 76:375–384PubMedGoogle Scholar
  16. 16.
    Nakamura M, Fujishima S, Sawafuji M, Ishizaka A, Oguma T, Soejima K, Matsubara H, Tasaka S, Kikuchi K, Kobayashi K, Ikeda E, Sadick M, Hebert CA, Aikawa N, Kanazawa M, Yamaguchi K (2000) Importance of interleukin-8 in the development of reexpansion lung injury in rabbits. Am J Respir Crit Care Med 161:1030–1036PubMedGoogle Scholar
  17. 17.
    Andersson U, Bird G, Britton S, Palacios R (1981) Humoral and cellular immunity in humans studied at the cell level from birth to two years of age. Immunological Rev 57:5–38Google Scholar
  18. 18.
    Metinko A (2004) Neonatal pulmonary host defense mechanisms. In: Polin RA, Fox WW, Abman SH (eds) Fetal and neonatal physiology. Saunders, Philadelphia, pp 1620–1673Google Scholar
  19. 19.
    Lachmann B, Robertson B, Vogel J (1980) In vivo lung lavage as an experimental model of the respiratory distress syndrome. Acta Anaesthesiol Scand 24:231–236PubMedGoogle Scholar
  20. 20.
    Krause MF, Hoehn T (1999) Decrease in lung volume depends on end-expiratory pressure in a rabbit model of airway lavage. Respiration 66:259–264CrossRefPubMedGoogle Scholar
  21. 21.
    Krause MF, Schulte-Mönting J, Hoehn T (1998) Rate of surfactant administration influences lung function and gas exchange in a surfactant-deficient rabbit model. Pediatr Pulmonol 25:196–204CrossRefPubMedGoogle Scholar
  22. 22.
    Van der Bleek J, Plötz F, Van Overbeek F, Heikamp A, Beekhuis H, Wildevuur C, Okken A, Bambang Oetomo S (1993) Distribution of exogenous surfactant in rabbits with severe respiratory failure: the effect of volume. Pediatr Res 34:154–158PubMedGoogle Scholar
  23. 23.
    Krause MF, Jäkel C, Haberstroh J, Schulte-Mönting J, Leititis JU, Orlowska-Volk M (2001) Alveolar recruitment promotes homogenous surfactant distribution in a piglet model of lung injury. Pediatr Res 50:34–43PubMedGoogle Scholar
  24. 24.
    Schiffmann H, Erdlenbruch B, Singer D, Singer S, Herting E, Hoeft A, Buhre W (2002) Assessment of cardiac output, intravascular volume status, and extravascular lung water by transpulmonary indicator dilution in critically ill neonates and infants. J Cardiothorac Vasc Anesth 16:592–597CrossRefPubMedGoogle Scholar
  25. 25.
    Scholtes U, Wiegand N, Zwirner J, Herting E (2002) Influence of porcine natural modified surfactant on chemotaxis and oxidative metabolism of polymorphonuclear leukocytes. Immunobiol 205:290–302Google Scholar
  26. 26.
    Schröder JM, Mrowietz U, Morita E, Christophers E (1987) Purification and partial biochemical characterization of a human monocyte-derived, neutrophil-activating peptide that lacks interleukin 1 activity. J Immunol 139:3474–3483PubMedGoogle Scholar
  27. 27.
    Baughman RP, Henderson RF, Whitsett J, Gunther KL, Keeton DA, Waide JJ, Zaccardelli DS, Pattishall EN, Rashkin MC (2002) Surfactant replacement for ventilator-associated pneumonia: a preliminary report. Respiration 69:57–62CrossRefPubMedGoogle Scholar
  28. 28.
    Ikegami M, Jobe AH (2002) Injury responses to different surfactants in ventilated premature lamb lungs. Pediatr Res 51:689–695CrossRefPubMedGoogle Scholar
  29. 29.
    Ali H, Richardson RM, Haribabu B, Snyderman R (1999) Chemoattractant receptor cross-desensitization. J Biol Chem 274:6027–6030CrossRefPubMedGoogle Scholar
  30. 30.
    Nakamura H, Yoshimura K, Jaffe HA, Crystal RG (1991) Interleukin-8 gene expression in human bronchial epithelial cells. J Biol Chem 266:19611–19617PubMedGoogle Scholar
  31. 31.
    Rolfe MW, Kunkel SL, Standiford TJ, Chensue SW, Allen RM, Evanoff HL, Phan SH, Strieter RM (1991) Pulmonary fibroblast expression of interleukin-8: a model for alveolar macrophage-derived cytokine networking. Am J Respir Cell Mol Biol 5:493–501PubMedGoogle Scholar
  32. 32.
    Chollet-Martin S, Jourdain B, Gibert C, Elbim C, Chastre J, Gougerot-Pocidalo MA (1996) Interactions between neutrophils and cytokines in blood and alveolar spaces during ARDS. Am J Respir Crit Care Med 153:594–601Google Scholar
  33. 33.
    Kiehl MG, Ostermann H, Thomas M, Muller C, Cassens U, Kienast J (1998) Inflammatory mediators in bronchoalveolar lavage fluid and plasma in leukocytopenic patients with septic shock-induced acute respiratory distress syndrome. Crit Care Med 26:1194–1199CrossRefPubMedGoogle Scholar
  34. 34.
    Shute JK, Vrugt B, Lindley IJD, Holgate ST, Bron A, Aalbers R, Djukanovic R (1997) Free and complexed interleukin-8 in blood and bronchial mucosa in asthma. Am J Respir Crit Care Med 155:1877–1883PubMedGoogle Scholar
  35. 35.
    Takasaki J, Ogawa Y (2001) Anti-interleukin-8 autoantibody in the tracheobronchial aspirate of infants with chronic lung disease. Pediatr Int 43:48–52CrossRefPubMedGoogle Scholar
  36. 36.
    Takasaki J, Ogawa Y (2000) Anti-IL-8 autoantibodies in the tracheobronchial aspirate of infants in the development of chronic lung disease. Acta Neonatol Jpn 36:1–5Google Scholar
  37. 37.
    Nielsen JB, Sjöstrand UH, Edgren EL, Lichtwarck-Aschoff M, Svensson BA (1991) An experimental study of different ventilatory modes in piglets in severe respiratory distress induced by surfactant depletion. Intensive Care Med 17:225–233PubMedGoogle Scholar
  38. 38.
    Von der Hardt K, Kandler MA, Fink L, Schoof E, Dötsch J, Brandenstein O, Bohle RM, Rascher W (2004) High frequency oscillatory ventilation suppresses inflammatory response in lung tissue and microdissected alveolar macrophages in surfactant depleted piglets. Pediatr Res 55:339–346CrossRefPubMedGoogle Scholar
  39. 39.
    Rotta AT, Gunnarsson B, Fuhrman BP, Hernan LJ, Steinhorn DM (2001) Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury. Crit Care Med 29:2176–2184CrossRefPubMedGoogle Scholar
  40. 40.
    Suh GY, Koh Y, Chung MP, An CH, Kim H, Jang WY, Han J, Kwon OJ (2002) Repeated derecruitments accentuate lung injury during mechanical ventilation. Crit Care Med 30:1848–1853CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Tobias Ankermann
    • 1
  • Tina Wiemann
    • 1
  • Anja Reisner
    • 1
  • Marzenna Orlowska-Volk
    • 2
  • Heike Köhler
    • 3
  • Martin F. Krause
    • 1
    Email author
  1. 1.Department of General PediatricsChristian-Albrechts UniversityKielGermany
  2. 2.Department of PathologyAlbert-Ludwigs UniversityFreiburgGermany
  3. 3.Federal Research Center for Viral Diseases of AnimalsJenaGermany

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