Drugs

, Volume 37, Supplement 1, pp 78–86 | Cite as

Effect of Nedocromil Sodium on Antigen-Induced Airway Responses in Allergic Sheep

  • William M. Abraham
Section 2: In Vivo Effects of Nedocromil Sodium in Human and Animal Models

Summary

We studied the effects of nedocromil sodium and sodium cromoglycate on early and late bronchial responses, the airway inflammation associated with the late response to inhaled Ascaris suum antigen in allergic sheep in vivo, and the antigen-induced contractile responses of sheep tracheal smooth muscle in vitro. In addition, we examined the effect of nedocromil sodium on the development of antigen-induced airway hyper-responsiveness in this model. Pretreatment with either nedocromil sodium or sodium cromoglycate was effective in blocking antigen-induced early and late responses in allergic sheep. Both drugs also prevented the influx of eosinophils into the airways, as assessed by bron-choalveolar lavage, observed during the late response in this model. No difference in drug potency was observed in vivo, but in vitro nedocromil sodium was 10- fold more potent than sodium cromoglycate against antigen-induced contractions of sheep tracheal smooth muscle. Nedocromil sodium was effective in blocking antigen-induced late responses and the subsequent development of airway hyper-responsiveness irrespective of whether the drug was given before antigen challenge or after the immediate response to antigen but before the late response. These findings indicate that nedocromil sodium is effective in the sheep model of asthma and therefore may be beneficial in the treatment of reversible obstructive airway disease in man.

Keywords

Late Response Carbachol Sodium Cromoglycate Airway Hyperresponsiveness Nedocromil 

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References

  1. Abraham WM, Delehunt JC, Yerger L, Marchette B. Characterization of a late phase pulmonary response following antigen challenge in allergic sheep. American Review of Respiratory Disease 128: 839–844, 1983PubMedGoogle Scholar
  2. Abraham WM. The importance of lipoxygenase products of arachidonic acid in allergen-induced late responses. American Review of Respiratory Disease 135: S49–S53, 1987PubMedGoogle Scholar
  3. Abraham WM, Stevenson JS, Chapman GA, Tallent MW. The effect of nedocromil sodium and cromolyn sodium on antigen-induced responses in allergic sheep in vivo and in vitro. Chest 92: 913–917, 1987PubMedCrossRefGoogle Scholar
  4. Abraham WM, Stevenson JS, Eldridge M, Garrido R, Nieves L. Nedocromil sodium in allergen-induced bronchial responses and airway hyperresponsiveness in allergic sheep. Journal of Applied Physiology 65(3): 1062–1068, 1988aPubMedGoogle Scholar
  5. Abraham WM, Sielczak MW, Wanner A, Perruchoud AP, Blinder L, Stevenson JS, et al. Cellular markers of inflammation in the airways of allergic sheep with and without allergen-induced late responses. American Review of Respiratory Disease 138: 1565–1571, 1988bPubMedGoogle Scholar
  6. Booij-Noord H, de Vries K, Sluiter HJ, Orie NGM. Late bronchial obstructive reaction to experimental inhalation of house dust extract. Clinical Allergy 20: 43–64, 1972Google Scholar
  7. Boschetto P, Fabbri LM, Zocca E, Milani G, Pivirotto F, Dal Vecchio A, et al. Prednisone inhibits late asthmatic reactions and airway inflammation induced by toluene diisocyanate in sensitized subjects. Journal of Allergy and Clinical Immunology 80: 261–267, 1987PubMedCrossRefGoogle Scholar
  8. Cartier A, Thomson NC, Frith PA, Roberts R and Hargreave FE. Allergen-induced increase in bronchial responsiveness to histamine: relationship to the late asthmatic response and change in airway caliber. Journal of Allergy and Clinical Immunology 70: 170–177, 1982PubMedCrossRefGoogle Scholar
  9. Cockcroft DW, Ruffin RE, Dolovich J, Hargreave FE. Allergen-induced increase in non-allergic bronchial reactivity. Clinical Allergy 7: 503–513, 1977PubMedCrossRefGoogle Scholar
  10. Cockcroft DW, Murdock KY. Comparative effects of inhaled salbutamol, sodium cromoglycate, and beclomethasone dipropionate on allergen-induced early asthmatic responses, late asthmatic responses, and increased bronchial responsiveness to histamine. Journal of Allergy and Clinical Immunology 79: 734–740, 1987PubMedCrossRefGoogle Scholar
  11. de Monchy JGR, Kauffman HF, Venge P, Koeter GH, Jansen HM, Sluiter HJ, de Vries K. Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions. American Review of Respiratory Disease 131: 373–376, 1985PubMedGoogle Scholar
  12. de Monchy JGR, Kauffman HF, Venge P, Koeter GH, de Vries K. Bronchoalveolar lavage and the late asthmatic reaction. In Kay AB (Ed.) Asthma: clinical pharmacology and therapeutic progress, pp. 46–57, Blackwell Scientific Publications, Oxford, 1986Google Scholar
  13. Delehunt JC, Perruchoud AP, Yerger L, Marchette B, Stevenson JS, Abraham WM. The role of SRS-A in the late bronchial response following antigen challenge in allergic sheep. American Review of Respiratory Disease 130: 748–754, 1984PubMedGoogle Scholar
  14. Durham SR, Lee TH, Cromwell O, Shaw RJ, Merrett TG, Merrett J, et al. Immunologic studies in allergen-induced late phase asthmatic reactions. Journal of Allergy and Clinical Immunology 74(1): 49–60, 1984PubMedCrossRefGoogle Scholar
  15. Durham SR, Kay AB. Inflammatory cells and mediators in allergen-induced late-phase asthmatic reactions. In Kay AB(Ed.) Asthma: clinical pharmacology and therapeutic progress, pp. 33–45, Blackwell Scientific Publications, Oxford, 1986Google Scholar
  16. Fabbri LM, Boschetto P, Zocca E, Milani G, Pivirotto F, Plebani M, et al. Bronchoalveolar neutrophilia during late asthmatic reactions induced by toluene diisocyanate. American Review of Respiratory Disease 136: 36, 1987PubMedCrossRefGoogle Scholar
  17. Kirby JG, Hargreave FE, O’Byrne PM. Indomethacin inhibits allergen-induced airway hyperresponsiveness but not allergen-induced asthmatic responses. American Review of Respiratory Disease 135: A312, 1987Google Scholar
  18. Lanes S, Stevenson JS, Codias E, Hernandez A, Sielczak MW, Wanner A, Abraham WM. Indomethacin and FPL-57231 inhibit antigen-induced airway hyperresponsiveness in sheep. Journal of Applied Physiology 61: 864–872, 1986PubMedGoogle Scholar
  19. Marsh WR, Irvin CG, Murphy KR, Behrens BL, Larsen GL. Increases in airway reactivity to histamine and inflammatory cells in bronchoalveolar lavage after the late asthmatic response in an animal model. American Review of Respiratory Disease 131: 875–879, 1985PubMedGoogle Scholar
  20. Mattoli S, Foresi A, Corbo GM, Valente S, Giuliano C. Effects of two doses of cromolyn on allergen-induced late asthmatic response and increased responsiveness. Journal of Allergy and Clinical Immunology 79: 747–754, 1987PubMedCrossRefGoogle Scholar
  21. Murphy KR, Wilson MC, Irvin CG. The requirement for polymorphonuclear leukocytes in the asthmatic response and heightened airway reactivity in an asthmatic model. American Review of Respiratory Disease 134: 62–68, 1986PubMedGoogle Scholar
  22. Naclerio RM, Proud D, Togias AG, Adkinson NF, Meyers DA, Kagey-Sobotka A, et al. Inflammatory mediators in late antigen-induced rhinitis. New England Journal of Medicine 313: 65–70, 1985PubMedCrossRefGoogle Scholar
  23. Nagy L, Lee TH, Kay AB. Neutrophil chemotactic activity in antigen-induced late asthmatic reactions. New England Journal of Medicine 306: 497–501, 1982PubMedCrossRefGoogle Scholar
  24. O’Byrne PM, Dolovich J, Hargreave FE. State of art: late asthmatic responses. American Review of Respiratory Disease 136: 740–751, 1987PubMedCrossRefGoogle Scholar
  25. Pepys J, Hutchcroft BJ. Bronchial provocation tests in the etiologic diagnosis and analysis of asthma. American Review of Respiratory Disease 112: 829–859, 1975PubMedGoogle Scholar

Copyright information

© ADIS Press Limited 1989

Authors and Affiliations

  • William M. Abraham
    • 1
  1. 1.Department of ResearchHarry Pearlman Biomedical Research Institute, Mount Sinai Medical CenterMiami BeachUnited States

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