Skip to main content
SpringerLink
Log in

Animal models for testing anti-inflammatory drugs for treatment of bronchial hyperreactivity in asthma

  • Reviews
  • Published:
Pharmaceutisch Weekblad Aims and scope Submit manuscript

Abstract

In the first part of this review the important role played by the bronchial hyperreactivity caused by chronic bronchopulmonary inflammation in asthma is described. Deliberately, more emphasis is placed on the role of pro-inflammatory eosinophils, alveolar macrophages, lymphocytes and platelets rather than on mast cells and neutrophils or the numerous mediators. The reason for this is that, on account of the large number of mediators and their multitude of functions and interactions in asthma, antagonism of a specific mediator will probably not be clinically relevant for optimally effective curative treatment of asthma. Inhibition of the infiltration and activation of pro-inflammatory cells is likely to be a more successful approach. In the second part, various animal models of bronchial hyperreactivity, which could be suitable for testing anti-asthmatic drugs, are discussed. Most animal models pay too little attention to chronic bronchopulmonary inflammation as the cause of bronchial hyperreactivity in asthma. In various models the bronchial hyperreactivity is provoked by a single mediator and this leads to selection of specific antagonists which are unlikely to be of clinical benefit. Rats appear to have certain advantages over guinea-pigs as experimental animals for bronchial hyperreactivity.

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

Access this article

Log in via an institution

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

References

  1. Williams MH, Shim CS. Clinical evaluation of asthma. In: Weiss EB, Segal MS, Stein M, eds. Bronchial asthma mechanisms and therapeutics. Boston: Little Brown & Company, 1985:310–9.

    Google Scholar 

  2. Riedel F, Rieger CHL. Asthma bronchiale im Kindesalter — eine aktuelle übersicht. Prax Klin Pneumol 1987;41:242–58.

    PubMed  Google Scholar 

  3. Hargreave FE, Ryan G, Thomson NC, O'Byrne PM, Latimer K, Juniper EF, et al. Bronchial hyperresponsiveness to histamine or methacholine in asthma: measurement and clinical significance. J Allergy Clin Immunol 1981;68:347–55.

    Article  PubMed  Google Scholar 

  4. Cockcroft DW, Killian DN, Mellon JJA, Hargreave FE. Bronchial reactivity to inhaled histamine: a method and clinical survey. Clin Allergy 1977;7:235–43.

    PubMed  Google Scholar 

  5. Borish L. The inflammatory theory of asthma. Immunol Invest 1987;16:501–32.

    PubMed  Google Scholar 

  6. Laitinen LA, Heino M, Laitinen A, Kava T, Haahtela T. Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am Rev Respir Dis 1985;131:599–606.

    PubMed  Google Scholar 

  7. Aizawa H, Miyazaki N, Shigematsu N, Tomooka M. A possible role of airway epithelium in modulating hyperresponsiveness. Br J Pharmacol 1988;93:139–45.

    PubMed  Google Scholar 

  8. Brunelleschi S, Haye-Legrand I, Labat C, Norel X, Benveniste J, Brink C. Platelet-activating-factoracether-induced relaxation of guinea pig airway muscle: role of prostaglandin E2 and the epithelium. J Pharmacol Exp Ther 1987;243:356.

    PubMed  Google Scholar 

  9. Tschirhart E, Frossard N, Bertrand C, Landry Y. Arachidonic acid metabolites and airway epithelium dependent relaxant factor. J Pharmacol Exp Ther 1987;243:310.

    PubMed  Google Scholar 

  10. Nijkamp FP. Hyperreactivity, inflammation and theΒ-receptor. In: Bonta IL, Bray MA, Parnham MJ, eds. The pharmacology of inflammation. Amsterdam: Elsevier Science Publishers, 1985:335–54. (Handbook of inflammation; vol 5).

    Google Scholar 

  11. Boushey HA, Holtzman MJ, Sheller JR, Nadel JA. Bronchial hyperreactivity. Am Rev Respir Dis 1980;121:389–413.

    PubMed  Google Scholar 

  12. Rademaker B. The regulation ofΒ-receptor function [dissertation]. Amsterdam: Free Univ, 1987.

    Google Scholar 

  13. Chieira C, Leite ACP, Oliveira L, Chieira L, Todo-Bom A, Loureiro C, et al. HumanΒ 2-adrenoceptors in asthmatics. Eur Respir J 1988;1(Suppl 2):317S.

    Google Scholar 

  14. Barnes PJ. New concepts in the pathogenesis of bronchial hyperresponsiveness. In: Schmitz-Schumann M, Menz G, Page CP, eds. PAF, platelets and asthma. Basle: BirkhÄuser Verlag, 1987:225–37.

    Google Scholar 

  15. Dahl R, Fredens K, Dybdal H, Tottrup A. The cytotoxicity of the eosinophil cationic protein. Allergy 1988;43 (Suppl 7):69.

    Google Scholar 

  16. Pliss LB, Tugenito EP, Ingram RH. Airway responsiveness, inflammation and effects of deep inhalation on airway obstruction in mild asthma. Am Rev Respir Dis 1989;139(Suppl):A227.

    Google Scholar 

  17. Schellenberg RR. Pathological changes contributing to airway hyperresponsiveness [Abstract]. In: Airway hyperreactivity: is it really important for asthma? Part 1 (Book of abstracts); 1989 Feb 26–27; London. London: IBC Technical Services, 1989.

    Google Scholar 

  18. Qian S, Mitzner W.In vivo andin vitro lung reactivity in elastase-induced emphysema in hamsters. Am Rev Respir Dis 1989;140:1549–55.

    PubMed  Google Scholar 

  19. Bellofiore S, Eidelman DH, Macklem PT, Martin JG. Effects of elastase-induced emphysema on airway responsiveness to methacholine in the rats. J Appl Physiol 1989;66:606–12.

    PubMed  Google Scholar 

  20. Mitchell HW. Bronchial hyperresponsiveness and airway narrowing: some theoretical considerations [Abstract]. In: Airway hyperreactivity: is it really important for asthma? Part 1 (Book of abstracts); 1989 Feb 26–27; London. London: IBC Technical Services, 1989.

    Google Scholar 

  21. Mitchell HW, Willet KE, Sparrow MP. Perfused bronchial segment and bronchial strip: narrowing vs. isometric force by mediators. J Appl Physiol 1989;60:2704–9.

    Google Scholar 

  22. Beasley R, Roche WR, Roberts JA, Holgate ST. Cellular events in the bronchi in mild asthma and after bronchial provocation. Am Rev Respir Dis 1989;139:806–17.

    PubMed  Google Scholar 

  23. Wardlaw AJ, Dunette S, Gleich GJ, Collins JV, Kay AB. Eosinophils and mast cells in bronchoalveolar lavage in subjects with mild asthma. Am Rev Respir Dis 1988;137:62–9.

    PubMed  Google Scholar 

  24. Corrigan CJ, Kay AB. CD 4 T-lymphocyte activation in acute severe asthma. Am Rev Respir Dis 1990;141:970–7.

    PubMed  Google Scholar 

  25. Frigas E, Gleich GJ. The eosinophil and the pathology of asthma. J Allergy Clin Immunol 1986;77:527–37.

    Article  PubMed  Google Scholar 

  26. O'Byrne PM, Dolovich J, Hargreave FE. Late asthmatic responses. Am Rev Respir Dis 1987;136:740–51.

    PubMed  Google Scholar 

  27. Metzger JW, Zavala D, Richerson HB, Moseley P, Iwamota P, Monick M, et al. Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs. Am Rev Respir Dis 1987;135:433–40.

    PubMed  Google Scholar 

  28. De Monchy JGR, Kaufmann HF, Venge P, KoËter GH, Jansen HM, Sluiter HJ, et al. Bronchoalveolar eosinophilia during allergen-induced late asthmatic reactions. Am Rev Respir Dis 1985;131:373–6.

    PubMed  Google Scholar 

  29. Gonzalez MC, Diaz P, Galleguillos FR, Ancic P, Cromwell O, Kay AB. Allergen induced recruitment of bronchoalveolar helper (OKT4) and suppressor (OKT8) T-cells in asthma. Am Rev Respir Dis 1987;136:600–4.

    PubMed  Google Scholar 

  30. Diaz P, Gonzalez C, Galleguilos F, Ancic P, Cromwell O, Kay AB. Leucocytes and mediators in bronchial mucus and bronchoalveolar lavage during allergeninduced late-phase asthmatic reactions. J Allergy Clin Immunol 1987;79:256.

    Google Scholar 

  31. Cookson WOCM, Craddock CF, Benson MK, Durham SR. Falls in peripheral eosinophil counts parallel the late asthmatic response. Am Rev Respir Dis 1989;139:458–62.

    PubMed  Google Scholar 

  32. Durham SR, Loegering DA, Gleich GJ, Kay AB. Eosinophils, non-specific bronchial responsiveness, and allergen-induced late-phase asthmatic reactions. J Allergy Clin Immunol 1985;75(Suppl 148):173.

    Article  Google Scholar 

  33. Horn BR, Robin ED, Theodore J, Van Kessel A. Total eosinophil counts in the management of bronchial asthma. N Engl J Med 1975;292:1152–5.

    PubMed  Google Scholar 

  34. Frigas E, Gleich GJ. Eosinophils in bronchial asthma. In: Michel FB, Bousquet J, Godard P, eds. Highlights in astmology. Heidelberg: Springer-Verlag, 1987:201–11.

    Google Scholar 

  35. Flavahan NA, Slifman NR, Gleich GJ, Vanhoutte PM. Human eosinophil major basic protein causes hyperreactivity of respiratory smooth muscle. Am Rev Respir Dis 1988;138:685–8.

    PubMed  Google Scholar 

  36. Gleich GJ, Flavahan NA, Fujisawa T, Vanhoutte PM. The eosinophil as a mediator of damage to respiratory epithelium: a model for bronchial hyperreactivity. J Allergy Clin Immunol 1988;81:761–81.

    Article  PubMed  Google Scholar 

  37. Shult PA, Lega M, Jadidi S, Vrtis R, Warner T, Graziano FM, et al. The presence of hypodense eosinophils and diminished chemiluminescence response in asthma. J Allergy Clin Immunol 1988;81:429–37.

    PubMed  Google Scholar 

  38. Fukuda T, Numao T, Akutsu I, Makino S. Possible existence of PAF receptors subtypes on human eosinophils and neutrophils. J Allergy Clin Immunol 1989;83:193.

    Google Scholar 

  39. Dahl R, Venge P, Fredens F. Eosinophils. In: Barnes PJ, Rodger IW, Thomson NC, eds. Asthma: basic mechanisms and clinical management. London: Academic Press, 1988:115–30.

    Google Scholar 

  40. Fels AOS, Cohn ZA. The alveolar macrophage. J Appl Physiol 1986;60:353–69.

    PubMed  Google Scholar 

  41. Tonnel AB, Joseph M, Capron A. Alveolar macrophage and allergic asthma. In: Kay AB, ed. Allergy and inflammation. London: Academic Press, 1987:139–50.

    Google Scholar 

  42. Rankin JA. The contribution of alveolar macrophages to hyperreactive airway disease. J Allergy Clin Immunol 1989;83:722–9.

    PubMed  Google Scholar 

  43. Capron M, Capron A. The IgE receptor of human eosinophils. In: Kay AB, ed. Allergy and inflammation. London: Academic Press, 1987:151–9.

    Google Scholar 

  44. MacDermot J, Fuller RW. Macrophages. In: Barnes PJ, Rodger IW, Thomson NC, eds. Asthma: basic mechanisms and clinical management. London: Academic Press, 1988:97–114.

    Google Scholar 

  45. Azzawi M, Bradley B, Wardlaw AJ, Frew AJ, Collins JV, Jeffery PK, et al. T Lymphocytes and activated eosinophils in bronchial biopsies from stable asthmatic subjects. Am Rev Respir Dis 1989;139(Suppl):A481.

    Google Scholar 

  46. Michel FB, Godard Ph, Bousquet J. Usefulness of bronchoalveolar lavage in asthma. Int Arch Allergy Appl Immunol 1989;88:101–7.

    PubMed  Google Scholar 

  47. Frew AJ, Kay AB. Interactions between lymphoid cells, mast cells and granulocytes in allergic inflammation [Abstract]. In: XIVth Congress of the European Academy of Allergology and Clinical Immunology (Book of abstracts); 1989 Sep 17–22; Berlin:81–4.

  48. Kay AB. The lymphocyte as an effector cell on allergic responses. Annual Conference of the British Society of Allergy and Clinical Immunology; 1989 Sep 13–15 (Book of abstracts); Edinburgh.

  49. Page CP. The involvement of platelets in nonthrombotic processes. TiPS 1988;9:66–71.

    PubMed  Google Scholar 

  50. Bernstein IL. Cromolyn-sodium and cromolyn-like drugs. In: Weiss EB, Segal MS, Stein M, eds. Bronchial asthma mechanisms and therapeutics. Boston: Little Brown & Company, 1985:724–33.

    Google Scholar 

  51. Morley J, Page CP, Sanjar S. Antiallergika bei Asthma. Triangel 1985;24(1/2):59–71.

    Google Scholar 

  52. Howarth PH, Durham SR, Kay BK, Holgate ST. The relationship between mast cell-mediator release and bronchial reactivity in allergic asthma. J Allergy Clin Immunol 1987;80:703–11.

    Article  PubMed  Google Scholar 

  53. Kay AB, Wardlaw AJ, Moqbel R, Buchanan DR, Cromwell O, Fitzharris P. Leukocytes and the asthma process. In: Kay AB, ed. Allergy and inflammation. London: Academic Press, 1987:203–23.

    Google Scholar 

  54. Bellofiore S, Martin JG. Antigen challenge of sensitised rats increases airway responsiveness to methacholine. J Appl Physiol 1988;65:1642–6.

    PubMed  Google Scholar 

  55. Eidelman DH, Bellofiore S, Martin JG. Late airway responses to antigen challenge in sensitised inbred rats. Am Rev Respir Dis 1988;137:1033–7.

    PubMed  Google Scholar 

  56. Linssen MJH. Animal models for the selection of antiinflammatory compounds for the treatment of bronchial hyperreactivity in asthma [dissertation]. Amsterdam: Free Univ, 1990.

    Google Scholar 

  57. Church MK, Hutson PA, Sanjar S, Holgate ST. Investigations into the role of neutrophils in early and late asthmatic responses in the guinea pig. In: Kay AB, ed. 7th Symposium of CIA: Allergy and inflammation; 1988 Mar 5–10; Martinique. Basle: Karger, 1988.

    Google Scholar 

  58. Holgate ST, Hutson PA, Shute JK, Rimmer SJ, Akerman CL, Church MK. The role of neutrophils and eosinophils in a model of asthma in the guinea pig. In: Symposium on eosinophils, allergy and asthma; 1988 Dec 7–8; London:10/2-4.

  59. Hutson PA, Church MK, Clay TP, Miller P, Holgate ST. Early and late-phase bronchoconstriction after allergen challenge of nonanesthesized guinea pigs. Am Rev Respir Dis 1988;137:548–57.

    PubMed  Google Scholar 

  60. Hutson PA, Holgate ST, Church MK. Effect of WEB 2086 on early and late airways responses to ovalbumin challenge in conscious guinea pigs. Br J Pharmacol 1988;95:770P.

    Google Scholar 

  61. Hutson PA, Holgate ST, Church MK. The effect of cromolyn sodium and salbuterol on early and late phase bronchoconstriction and airway leukocyte infiltration after allergen challenge of nonanesthesized guinea pigs. Am Rev Respir Dis 1988;138:1157–63.

    PubMed  Google Scholar 

  62. Clay TP. Allergen-induced late responses in the guinea pig. Use for pharmacological investigations. In: 3rd Meeting of the British Inflammation Research Association; 1989 Mar 29; Dagenham.

  63. Konno A, Terada N, Okamoto Y. Changes of adrenergic and muscarinic cholinergic receptors in nasal mucosa in nasal allergy. ORL 1987;49:103–11.

    PubMed  Google Scholar 

  64. Lellouch-Tubiana A, Lefort J, Simon MT, Pflister F, DaLage C, Vargaftig BB. Comparison of the eosinophilotactic effect of PAF-acether and antigenin vivo: role of PAF-acether antagonists and platelets. Prostaglandins 1987;34:168.

    Article  Google Scholar 

  65. Dunn CJ, Elliott GA, Oostveen JA, Richards IM. Development of a prolonged eosinophil-rich inflammatory leukocyte infiltration in the guinea pig asthmatic response to ovalbumin inhalation. Am Rev Respir Dis 1988;137:541–7.

    PubMed  Google Scholar 

  66. Ijima H, Ishii M, Yamauchi K, Chao CL, Kimura K, Shimura S, et al. Bronchoalveolar lavage and histological characterization of late asthmatic response in the guinea pig. Am Rev Respir Dis 1987;136:922–9.

    PubMed  Google Scholar 

  67. Bachelet M, Dumarey C, Lefort J, Lellouch-Tubiana A, Pretolani M, Vargaftig BB. Guinea-pig lung as a model to study non-specific hyperresponsiveness started by active immunisation: a hypothesized role for PAF-cether and inflammatory cells. In: 17th Symposium of CIA: Allergy and inflammation; 1988 Mar 5–10; Martinique. Basle: Karger, 1988.

    Google Scholar 

  68. Fügner A. Formation of oedema and accumulation of eosinophils in the guinea pig lung. Int Arch Allergy Appl Immunol 1989;88:225–7.

    PubMed  Google Scholar 

  69. Pretolani M, Lefort J, Dumarey C, Vargaftig BB. Role of lipoxygenase metabolites for the hyperresponsiveness to platelet-activating-factor of lungs from actively sensitised guinea pigs. J Pharmacol Exp Ther 1989;248:353–9.

    PubMed  Google Scholar 

  70. Shampain MP, Behrens LB, Larsen GL, Henson PM. An animal model of late pulmonary responses toAlternaria challenge. Am Rev Respir Dis 1982;126:493–8.

    PubMed  Google Scholar 

  71. Metzger WJ, Sjoerdsma K, Brown L, Coyle T, Page C, Touvay C. The late phase asthmatic response in the allergic rabbit: a role for PAF and modification by PAF antagonist, ginkgolide BN 52021. In: Braquet P, ed. New trends in lipid mediators research. Vol. 2. Basle: Karger, 1988:40–58.

    Google Scholar 

  72. Marsh WR, Irvin CG, Murphy KR, Beherens BL, Larsen GL. 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 1985;131:875–9.

    PubMed  Google Scholar 

  73. Murphy KR, Giezen L, Marsh JR, Graves J, Larsen GJ. The effect of polymorphonuclear leukocytes (PML) depletion on the late asthmatic response (LAR). J Allergy Clin Immunol 1985;75(1 pt 2):148.

    Article  Google Scholar 

  74. Page CP, Coyle AJ, Brown LA, Touvay C, Metzger WJ. The contribution of platelets and PAF to allergeninduced late-onset responses and bronchial hyperreactivity in allergic rabbits. Prostaglandins 1988;35:800.

    Article  Google Scholar 

  75. Buckner CK, Songsiridej V, Dick EC, Busse WW.In vivo andin vitro studies on the use of the guinea-pig as a model for virus-provoked airway hyperreactivity. Am Rev Respir Dis 1985;132:305–10.

    PubMed  Google Scholar 

  76. Folkerts G, Nijkamp FP. Broncho-alveolar cells from virus infected guinea pigs induce airway hyperreactivity. In: Nijkamp FP, Engels F, Henricks PAJ, Van Oosterhout AJM, eds. Mediators in airway hyperreactivity. The Hague: 1990:06.

  77. Lemanske RF, Kaliner MA. The experimental production of increased eosinophils in rat late-phase reaction. Immunology 1982;45:561–8.

    PubMed  Google Scholar 

  78. Laycock SM, Smith H, Spicer BA. Airway hyperreactivity and blood, lung and airway eosinophilia in rats treated with sephadex particles. Int Arch Allergy Appl Immunol 1987;82:347–51.

    PubMed  Google Scholar 

  79. Walls RS, Beeson PB. Mechanisms of eosinophilia. IX. Induction of eosinophilia by certain forms of dextran. Proc Soc Exp Biol Med 1972;140:689–93.

    PubMed  Google Scholar 

  80. Schriber RA, Zucker-Franklin D. A method for the induction of blood eosinophilia with simple protein antigens. Cell Immunol 1974;14:470–4.

    Article  PubMed  Google Scholar 

  81. Eady RP, Trigg S, Orr TSC. Anaphylactic bronchoconstriction in rats immunized with antigen-coated latex particles. Clin Exp Immunol 1978;32:283–9.

    PubMed  Google Scholar 

  82. Linssen MJH, Wilhelms O-H. Chemiluminescence of bronchoalveolar lavage cells as an indicator of leukocyte activation in rats with a hyperreactive bronchus. J Biolum Chemilum 1990;5:65–9.

    Article  Google Scholar 

  83. Linssen MJH, Lemmermann Ch, Lipponer L, Wilhelms O-H. Late phase increase of thrombin-like proteinase (THROLP), protein, leukocytes (BAL) in bronchoalveolar lavage (BALF), and chemiluminescence (CL) of BAL after ovalbumin aerosol inhalation by actively immunized rats. Int Arch Appl Immunol. In press.

  84. Van Oosterhout AJM, Folkerts G, Ten Have GAM, Nijkamp FP. Involvement of the spleen in the endotoxin-induced deterioration of the respiratory airway and lymphocyteΒ-adrenergic systems of the guinea-pig. Eur J Pharmacol 1988;147:421–30.

    Article  PubMed  Google Scholar 

  85. Olsen UB, Bille-Hansen V. Endotoxin pretreatment enhances neutrophil FMLP-receptor binding and activity in guinea pigs. Agents Actions 1987;21(1/2):177–9.

    Article  PubMed  Google Scholar 

  86. Folkerts G, Engels F, Nijkamp FP. Endotoxin-induced hyperreactivity of the guinea pig isolated trachea coincides with decreased prostaglandin E2 production by the epithelial layer. Br J Pharmacol 1989;96:388–94.

    PubMed  Google Scholar 

  87. Folkerts G, Engels F, Nijkamp FP. Respiratory airway activity coincides with decreased epithelium-derived PGE2. Agents Actions 1989;26(1/2):68–9.

    PubMed  Google Scholar 

  88. Folkerts G, Henricks PAJ, Slootweg PJ, Nijkamp FP. Endotoxin-induced inflammation and injury of the guinea-pig respiratory airways cause bronchial hyporeactivity. Am Rev Respir Dis 1988;137:1441–8.

    PubMed  Google Scholar 

  89. Folkerts G, Henricks PAJ, Nijkamp FP. Inflammatory reactions in the respiratory airways of the guinea pig do not necessarily induce bronchial hyperreactivity. Agents Actions 1988;23(1/2):94–5.

    Article  PubMed  Google Scholar 

  90. Beyer L, Botting J, Crook P, Oyekan AO, Page CP, Rylander R. The involvement of platelet activating factor in endotoxin-induced pulmonary platelet recruitment in the guinea-pig. Br J Pharmacol 1987;92:803–8.

    PubMed  Google Scholar 

  91. Rylander R, Beyer L, Lantz RC, Burell R, Sedivy P. Modulation of pulmonary inflammation after endotoxin inhalation with a platelet-activating antagonist (48740 RP). Int Arch Appl Immunol 1988;86:303–7.

    Google Scholar 

  92. Pauwels R. Effect of inflammation on bronchial hyperresponsiveness. In: Nadel JA, Pauwels R, Snashall PD, eds. Bronchial hyperresponsiveness. Oxford: Blackwell Scientific Publications, 1987:315–21.

    Google Scholar 

  93. Pauwels R. The clinical relevance of airway inflammation. Eur J Resp Dis 1986;69(Suppl):88–95.

    Google Scholar 

  94. Aizawa H, Chung KF, Leikauf GD, Ueki I, Bethel RA, O'Byrne PM, et al. Significance of thromboxane generation in ozone-induced airway hyperresponsiveness in dogs. J Appl Physiol 1985;59:1918–23.

    PubMed  Google Scholar 

  95. Aizawa H, Hirose T. A possible mechanism of airway hyperresponsiveness induced by prostaglandin F2α and thromboxane A2. Prostaglandins Leukot Essent Fatty Acids 1988;33:185–9.

    PubMed  Google Scholar 

  96. O'Byrne PM, Leikauf GD, Aizawa H, Bethel RA, Ueki IF, Holtzman MJ, et al. Leukotriene B4 induces airway hyperresponsiveness in dogs. J Appl Physiol 1985;59:1941–6.

    PubMed  Google Scholar 

  97. Vargaftig BB, Lefort J, Rotilio D. Route-dependent interactions between PAF-acether and guinea pig bronchopulmonary smooth muscle: relevance of cyclooxygenase mechanisms. In: Arnoux P, Benveniste J, eds. Platelet-activating factor. Amsterdam: Elsevier, 1983. (INSERM Symp. 23).

    Google Scholar 

  98. Bachelet M, Bureau M, Chignard M, Coeffier E, Cordeiro RB, Desquand S, et al. PAF-acether in inflammation and experimental asthma. In: Rand, Raper, eds. Proceedings of the Xth International Congress of Pharmacology (IUPHAR); 1987 Aug 23–28; Sydney. Amsterdam: Excerpta Medica, 1987.

    Google Scholar 

  99. Sanjar S, Smith D, Morley J, Mazzoni L, Tapparelli C. PAF Antagonism and the response to allergen. Thromb Haemost 1987;58:557.

    Google Scholar 

  100. Lellouch-Tubiana A, Lefort J, Simon MT, Pfister A, Vargaftig BB. Eosinophil recruitment into guinea pig lungs after PAF-acether and allergen administration. Am Rev Respir Dis 1988;137:948–54.

    PubMed  Google Scholar 

  101. Morley J, Page CP, Sanjar S. Antiallergika bei Asthma. Triangel 1985;24(1/2):59–71.

    Google Scholar 

  102. Andersson GP, Fennesy MR. Effects of REV 5901, a 5-lipoxygenase-inhibitor and leukotriene-antagonist, on pulmonary responses to platelet activating factor in the guinea-pig. Br J Pharmacol 1988;94:1115–22.

    PubMed  Google Scholar 

  103. Andersson GP, Fennesy MR. Lipoxygenase metabolites mediate increased airways responsiveness to histamine after acute platelet activating factor exposure in the guinea-pig. Agents Actions 1988;24 (1/2):8–19.

    Article  PubMed  Google Scholar 

  104. Andersson GP, White HL, Fennessy MR. Increased airway responsiveness to histamine induced by platelet activating factor in the guinea-pig: possible role of lipoxygenase metabolites. Agents Actions 1988;24 (1/2):1–7.

    Article  PubMed  Google Scholar 

  105. Andersson GP, Fennesy MR. Effect of REV 5901, a leukotriene inhibitor, on platelet activating factorinduced increased airways responsiveness to histamin in the guinea-pigin vivo. Clin Exp Pharmacol Physiol 1988;(Suppl 13):22.

    Google Scholar 

  106. Robertson DN, Coyle AJ, Rhoden KJ, Grandordy B, Page CP, Barnes PJ. The effect of platelet-activating factor on histamine and muscarinic receptor function in g.p airways. Am Rev Respir Dis 1988;137:1317–22.

    PubMed  Google Scholar 

  107. Heuer H, Casals Stenzel J. Effects of beta2-adrenoceptor agonist fenoterol (Berotec) and platelet activating factor on bronchial hyperreactivity in the guinea-pig. Clin Exp Pharmacol Physiol 1988;(Suppl 13):24.

    Google Scholar 

  108. Touvay C, Pignol B, Vilain B, Pflister A, Mencia-Huerta JM, Braquet P. Functional and morphologic alterations of guinea-pig lung induced by chronic infusion of platelet-activating factor (PAF-acether) support a role for the mediator in bronchial hyperreactivity. Prostaglandins 1987;34:180.

    Article  Google Scholar 

  109. Coyle AJ, Robertson DN, Page CP. The role of PAF in antigen-induced eosinophil accumulation in the lung. Prostaglandins 1987;34:169.

    Article  Google Scholar 

  110. Wylie F, Coyle AJ, Robertson DN, Page CP. The effect of heparin and heparin-related molecules on PAF-induced bronchial hyperreactivity in the guinea pig. Clin Exp Pharmacol Physiol 1988;(Suppl 13):23.

    Google Scholar 

  111. Roum JH, Murlas C. Ozone-induced changes in muscarinic bronchial reactivity by different testing methods. J Appl Physiol 1984;57:1783–9.

    PubMed  Google Scholar 

  112. Murlas C, Roum JH. Sequence of pathologic changes in the airway mucosa of guinea pigs during ozoneinduced bronchial hyperreactivity. Am Rev Respir Dis 1985;131:314–20.

    PubMed  Google Scholar 

  113. Cuss F, Barnes PJ. Epithelial mediators. Am Rev Respir Dis 1987;136(4 Part 2):S32–5.

    PubMed  Google Scholar 

  114. Murlas C, Roum JH. Bronchial hyperreactivity occurs in steroid-treated guinea pigs depleted of leukocytes by cyclophosphamide. J Appl Physiol 1985;58:1630–7.

    PubMed  Google Scholar 

  115. Evans TW, Brokaw JJ, Chung KF, Nadel JA, McDonald DM. Ozone-induced bronchial hyperresponsiveness in the rat is not accompanied by neutrophil influx or increased vascular permeability in the trachea. Am Rev Respir Dis 1988;138:140–4.

    PubMed  Google Scholar 

  116. Holroyde MC, Smith SY, Holme G. Analysis of antigen-induced changes in pulmonary mechanics in sensitized inbred rats. Can J Physiol Pharmacol 1982;60:644–51.

    PubMed  Google Scholar 

  117. Piechuta H, Ford-Hutchinson AW. Inhibition of allergen-induced bronchoconstriction in hyperreactive rats as a model for testing 5-lipoxygenase inhibitors and leukotriene D4 antagonists. Agents Actions 1987;22:69–74.

    Article  PubMed  Google Scholar 

  118. Piechuta H, Smith ME, Share NN, Holme G. The respiratory response of sensitised rats to challenge with aerosolized antigen. Immunology 1979;38:385–92.

    PubMed  Google Scholar 

  119. Holme G, Piechuta H. The derivation of an inbred line of rats which develop asthma-like symptoms following challenge with aerosolized antigen. Immunology 1981;42:19–21.

    PubMed  Google Scholar 

  120. Brunet G, Piechuta H, Hamel R, Holme G. Respiratory responses to leukotrienes and biogenic amines in normal and hyperreactive rats. J Immunol 1983;131:434–8.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Allergy Department FM-1M, Boehringer Mannheim GmbH, Sandhofer Strasse 116, 6800, Mannheim, FRG

    Marcel J. Linssen & Otto -Henning Wilhelms

  2. Department of Pharmacochemistry, Free University, De Boelelaan 1083, 1081, HV Amsterdam, the Netherlands

    Hendrik Timmerman

Authors
  1. Marcel J. Linssen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Otto -Henning Wilhelms
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hendrik Timmerman
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Linssen, M.J., Wilhelms, O.H. & Timmerman, H. Animal models for testing anti-inflammatory drugs for treatment of bronchial hyperreactivity in asthma. Pharmaceutisch Weekblad Scientific Edition 13, 225–237 (1991). https://doi.org/10.1007/BF02015576

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02015576

Keywords

Search

Navigation