Skip to main content
Log in

Effects of ketotifen on airway responses to allergen challenge in the actively sensitized Brown Norway rat

  • Allergy and Histamine
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

The purpose of the study was to examine the effect of ketotifen on the airway responses and the recruitment of the inflammatory cells into the airways of sensitized rats after antigen challenge. Twenty-five Brown Norway rats, 7–9 weeks old, were actively sensitized to ovalbumin (OA) (1 mg s.c.) andBordetella pertussis vaccine (109 bacilli i.p.) At 14 days after sensitization rats were anesthetized with urethane (1.1 g/kg i.p.) and intubated endotracheally. Aerosols of OA (5% W/V in saline for 5 min) were administered to control rats (Group A;n=9), to a low-dose ketotifen group (Group B; 1 mg/kg PO;n=8) and a high-dose ketotifen group (Group C; 10 mg/kg; PO for 10 days;n=9). Pulmonary resistance (R L) was measured at baseline, and every 15 min for up to 8 h after OA. The magnitude of the early response was 241±51% in A (% baselineR L; mean±SE), and significantly less in B (119±7%) and C (131±16%) (p<0.01). The late response was significantly lower in C than A but not B. The total cell number in bronchoalveolar lavage at 8 h after OA challenge was significantly higher in A than B and C (p<0.01). The lymphocyte and eosinophil counts were reduced in B and C compared to A (p<0.05). A positive correlation was found between the late response and total number of cells recovered in the BAL (r=0.78) (p<0.05). We conclude that ketotifen inhibited the early response and late response, and the influx of inflammatory cells into the airways after antigen challenge.

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.

Similar content being viewed by others

References

  1. M. Kaliner,Asthma and mast cell activation. J. Allergy Clin. Immunol.83, 510–520 (1989).

    PubMed  Google Scholar 

  2. D. W. Cockcroft, R. E. Ruffin, J. Dolovich and F. E. Hargreave,Allergen-induced increase in non-allergic bronchial reactivity. Allergy7, 503–513 (1977).

    PubMed  Google Scholar 

  3. M. P. Shampain, B. L. Behrens, G. L. Larsen and P. M. Henson,An animal model of late pulmonary response to alternaria challenge. Am. Rev. Respir. Dis.126, 493–498 (1982).

    PubMed  Google Scholar 

  4. W. M. Abraham, J. C. Delehunt, L. Yerger and B. Marchette,Characterization of a late phase pulmonary response following antigen challenge in allergic sheep. Am. Rev. Respir. Dis.128, 839–844 (1983).

    PubMed  Google Scholar 

  5. H. Iijima, M. Ishii, K. Yamauchi, et al.,Bronchoalveolar lavage and histological characterization of late asthmatic response in guinea pigs. Am. Rev. Respir. Dis.136, 922–929 (1987).

    PubMed  Google Scholar 

  6. R. Hamel, C. S. McFarlane and A. W. Ford-Hutchinson,Late pulmonary responses induced by Ascaris allergen in conscious squirrel monkeys. J. Appl. Physiol.61, 2081–2087 (1986).

    PubMed  Google Scholar 

  7. R. Pauwels, H. Bazin, B. Plateau and M. Van der Straeten,The influence of antigen dose on IgE production in different rat strains. Immunology36, 151–157 (1979).

    PubMed  Google Scholar 

  8. D. H. Eidelman, S. Bellofiore and J. G. Martin,Late airway responses to antigen challenge in sensitized inbred rats. Am. Rev. Respir. Dis.137, 1033–1037 (1988).

    PubMed  Google Scholar 

  9. L. P. Craps and U. M. Ney,Ketotifen: Current views on its mechanism of action and their therapeutic implications. Respiration45, 411–421 (1984).

    PubMed  Google Scholar 

  10. U. Martin and M. Baggiolini,Dissociation between the anti-anaphylactic and the anti-histaminic actions of ketotifen. Naunyn-Schmiedeberg's Arch. Pharmacol.316, 186–189 (1981).

    Google Scholar 

  11. M. Adachi, H. Kobayashi, N. Aoki, M. Iijima, F. Kokuby, A. Furuya and T. Takahashi,A comparison of the inhibitory effects of ketotifen and disodium cromoglycate on bronchial responses to house dust, with special reference to the late asthmatic response. Pharmatherapeutica4, 36–42 (1984).

    PubMed  Google Scholar 

  12. M. A. King, I. Chapman, A. Kristenssen, J. Sanjar and J. Morley,Human recombinant lymphokines and cytokines induce pulmonary eosinophilia in the guinea pig which is inhibited by ketotifen and AH 21-132. Arch. Allergy Appl. Immunol.91, 354–361 (1990).

    Google Scholar 

  13. S. Sapienza, D. H. Eidelman, P. M. Renzi and J. G. Martin,Role of leukotriene D4, in the early and late pulmonary responses of rats to allergen challenge. Am. Rev. Respir. Dis.142, 353–358 (1990).

    PubMed  Google Scholar 

  14. U. Martin and D. Roemer,The pharmacological properties of a new orally active anti-anaphylactic compound: Ketotifen, a benzocycloheptajiophene. Drug Res.28, 770–786 (1978).

    Google Scholar 

  15. B. Wuethrich, P. Radielovic and M. Debelic,The protective effects of a new oral anti-asthma (ketotifen, HC20-511) against experimentally induced bronchospasm 5 different models. Int. J. Clin. Pharmacol.16, 424–429 (1978).

    Google Scholar 

  16. S. Esau, J. Del Carpio and J. G. Martin,A comparison of the effects of ketotifen and clemastine on cutaneous and airway reactivity to histamine and allergen in atopic asthmatic subjects. J. Allergy Clin. Immunol.74, 270–274 (1984).

    PubMed  Google Scholar 

  17. D. P. Hutson, R. B. Bressler, M. Kaliner, L. K. Sowell and M. W. Baylor,Prevention of mast cell degranulation by ketotifen in patients with physical urticarias. Ann. Int. Med.104, 507–510 (1986).

    PubMed  Google Scholar 

  18. L. E. Mansfield, P. Taistra, J. Snatamauro, S. King and K. Andriano,Inhibition of dermographia, histamine and dextromethorphan skin tests by ketotifen. A possible effect on cutaneous vascular response to mediators. Ann. Allergy63, 201–206 (1989).

    PubMed  Google Scholar 

  19. H. Piechuta, A. W. Ford-Hutchinson and L. G. Letts,Inhibition of allergen-induced bronchoconstriction in hyperreactive rats as a model for testing 5-lipoxygenase inhibitors and leukotriene D 4 receptor antagonists. Agents and Actions22, 69–74 (1987).

    PubMed  Google Scholar 

  20. J. G. R. De Monchy, H. F. Kaufman, P. Venge, et al.,Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions. Am. Rev. Respir. Dis.131, 373–376 (1985).

    PubMed  Google Scholar 

  21. W. M. Abraham, M. W. Sielczak, A. Wanner, et al.,Cellular markers of inflammation in the airways of allergic sheep with and without allergen induced late responses. Am. Rev. Respir. Dis.138, 1565–1571 (1988).

    PubMed  Google Scholar 

  22. W. R. Marsh, C. G. Irvin, K. R. Murphy, B. L. Behrens and G. L. Larsen,Increases in airway reactivity to histamine and inflammatory cells in bronchoalveolar lavage after the late asthmatic response in an animal model. Am. Rev. Respir. Dis.131, 875–879 (1985).

    PubMed  Google Scholar 

  23. S.T. Blythe, D. England, B. Esser, P. Junk and R. F. Lemanske,IgE antibody mediated inflammation of rat lung: histologic and bronchoalveolar lavage assessment. Am. Rev. Respir. Dis.134, 1246–1251 (1986).

    PubMed  Google Scholar 

  24. P. A. Hutson, S. T. Holgate and M. K. Church,The effects of cromolyn sodium and albuterol on early and late phase bronchoconstriction and airway leukocyte infiltration after allergen challenge of non-anesthetized guinea pigs. Am. Rev. Respir. Dis.138, 1157–1163 (1988).

    PubMed  Google Scholar 

  25. J. C. Delehunt, A. P. Perruchoud, L. Yerger, B. Marchette, J. S. Stevenson and W. M. Abraham,The role of slowreacting substance of anaphylaxis in the late bronchial response after antigen challenge in allergic sheep. Am. Rev. Respir. Dis.130, 748–754 (1984).

    PubMed  Google Scholar 

  26. M. Joseph and A. Capron,IgE receptors on macrophages: Biological significance. Agents and Action16, 27–29 (1985).

    Google Scholar 

  27. J. a. Rankin, W. Hitchcock, M. K. Merrill, M. K. Bach, J. R. Brashler and P. W. Askenase,IgE dependent release of leukotriene C4 from alveolar macrophages. Nature (London)297, 329–331 (1982).

    Google Scholar 

  28. Y. Kakuta, T. Kaito, H. Sasaki and T. Takashima,Effect of ketotifen on human alveolar macrophages. J. Allergy Clin. Immunol.81, 469–474 (1988).

    PubMed  Google Scholar 

  29. W. Podleski, B. A. Panaszek, J. L. Schmidt and R. B. Burns,Inhibition of eosinophils degranulation by ketotifen in a patient with milk allergy, manifested as bronchial asthma —an electronic microscopic study. Agents and Actions15, 177–181 (1984).

    PubMed  Google Scholar 

  30. J. Morley, C. P. Page, L. Mazzoni and S. Sanjar,Effects of ketotifen upon responses to platelet activating factor: a basis for asthma prophylaxis. Ann. Allergy56, 335–340 (1986).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sapienza, S., Renzi, P.M. & Martin, J.G. Effects of ketotifen on airway responses to allergen challenge in the actively sensitized Brown Norway rat. Agents and Actions 37, 238–244 (1992). https://doi.org/10.1007/BF02028115

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02028115

Keywords

Navigation