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Anti-Inflammatory Drugs in Asthma: The Pathophysiology of Asthma

  • James L. Lordan
  • Ratko Djukanović
Chapter
  • 89 Downloads
Part of the Progress in Inflammation Research book series (PIR)

Abstract

Asthma is a chronic condition characterised by widespread, variable and reversible airflow obstruction which is either spontaneous or pharmacologically induced. The underlying pathophysiological feature of asthma is increased airway responsiveness which develops on a basis of diffuse bronchial inflammation. The prevalence of asthma is increasing worldwide despite improved treatment which has resulted from a more comprehensive understanding of its pathogenesis [1]. In most countries asthma affects between 4 and 8% of the population, with a trend towards an increase in morbidity as judged by increased hospital admissions [2]. The reasons for this are unclear, but environmental factors such as indoor and outdoor air pollution and changes in lifestyle are considered to be amongst the contributing factors.

Keywords

Mast Cell Airway Smooth Muscle Allergy Clin Immunol Respir Crit Human Bronchial Epithelial Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Davies RJ, Tang J, Abdelaziz MM et al (1997) New insights into the understanding of asthma. Chest 111: 2–10Google Scholar
  2. 2.
    Sandford A, Weir T, Pare Ph (1996) The genetics of asthma. Am J Respir Crit Care Med 153: 1749–1765PubMedGoogle Scholar
  3. 3.
    Mehlhop PD, Van de Rijn M, Goldberg AB et al (1997) Allergen-induced bronchial reactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma. Proc Natl Acad Sci USA 94: 1344–1349PubMedGoogle Scholar
  4. 4.
    Fahy JV, Fleming E, Wong HH et al (1997) The effect of an anti-IgE monoclonal antibody on the early-and late responses to allergen inhalation. Am J Respir Crit Care Med 155: 1828–1834PubMedGoogle Scholar
  5. 5.
    Corne J, Djukanovic R, Lynette T, Holgate ST et al (1997) The effect of intravenous administration of a chimeric anti-IgE antibody on serum IgE levels in atopic subjects: Efficacy, safety and pharmacokinetics. J Clin Invest 99: 879–887PubMedGoogle Scholar
  6. 6.
    Holgate ST (1997) Asthma: A dynamic disease of inflammation and repair. The rising trends in asthma. The Ciba Foundation Bulletin 206: 5–34Google Scholar
  7. 7.
    Morton NE (1996) Statistical consideration for genetic analysis of atopy and asthma, In: DA Meyers, SB Liggett (eds): The genetics of asthma. Marcel Dekker, New York, 367–378Google Scholar
  8. 8.
    Edfors-Lubs M (1971) Allergy in 7,000 twin pairs. Acta Allergol 26: 249–285PubMedGoogle Scholar
  9. 9.
    Cookson W, Sharp PA, Faux JA et al (1989) Linkage between IgE responses underlying asthma and rhinitis and chromosome 11q13. Lancet 1: 1292–1295PubMedGoogle Scholar
  10. 10.
    Young RP, Lynch J, Sharp PA et al (1992) Confirmation of genetic linkage between atopic IgE responses and chromosome 11q13. J Med Genetics 29: 236–238Google Scholar
  11. 11.
    Sandford AJ, Shirakawa T, Moffatt MF (1993) Localisation of atopy and the β subunit of the high affinity IgE receptor(FcεRI) on chromosome 11q13. Lancet 341: 332–334PubMedGoogle Scholar
  12. 12.
    Manian P (1997) Genetics of asthma: A review. Chest 112: 1397–1408PubMedGoogle Scholar
  13. 13.
    Shirakawa T, Li A, Dubowitz M et al (1994) Association between atopy and variants of the β subunit of the high affinity IgE receptor. Nat Genetics 7: 125–130Google Scholar
  14. 14.
    Hill MR, Cookson W (1996) A new variant of the β subunit of the high affinity receptor for IgE (FcεRI-β E237G): associations with measures of atopy and bronchial hyper-reponsiveness. Hum Mol Genet 5: 959–962PubMedGoogle Scholar
  15. 15.
    Chandrashekharappa SC, Rebelesky MS, Firak TA et al (1990) A long range restriction map of the interleukin-4 and IL-5 linkage group on chromosome 5. Genomics 6: 94–99Google Scholar
  16. 16.
    Marsh DG, Neely JD, Breazeale DR et al (1994) Linkage analysis of IL-4 and other chromosome 5q31.1 markers and total serum IgE concentrations. Science 264: 1152–1156PubMedGoogle Scholar
  17. 17.
    Meyers DA, Postma DS, Panhuysen CIM et al (1994) Evidence for a locus regulating total serum IgE mapping to chromosom 5. Genomics 23: 464–470PubMedGoogle Scholar
  18. 18.
    Postma DS, Bleecker ER, Amelung PJ et al (1995) Genetic susceptibility to asthma-bronchial hyperresponsiveness co-inherited with a major gene for atopy. N Engl J Med 333: 894–900PubMedGoogle Scholar
  19. 19.
    Barnes KC, Neely JD, Duffy DL et al (1996) Linkage of asthma and total IgE concentration to markers on chromosome 12q: evidence from Afro-Carribean and Caucasian populations. Genomics 37: 41–50PubMedGoogle Scholar
  20. 20.
    Wilkinson J, Thomas S, Loi P et al (1996) Evidence for linkage for atopy and asthma to markers on chromosome 12q. Eur Respir J 9: 435sGoogle Scholar
  21. 21.
    Howell WM, Holgate ST (1995) HLA genetics and allergic disease. Thorax 50: S15–S18Google Scholar
  22. 22.
    Hsieh K, Shieh C, Hsieh R et al (1991). Association of HLA-DQw2 with Chinese childhood asthma. Tissue antigens 38: 181–182PubMedGoogle Scholar
  23. 23.
    Bignon JS, Yolande A, Ju L et al (1994) HLA class II alleles in isocyanate-induced asthma. Am J Respir Grit Care Med 149: 71–75Google Scholar
  24. 24.
    Moffatt MF, Hill MR, Cornelis F et al (1994) Genetic kinkage of T cell receptor α/δ complex to specific IgE responses. Lancet 343: 1597–1600PubMedGoogle Scholar
  25. 25.
    Rosenwasser LJ (1997) Genetics of atopy and asthma: promoter-based candidate gene studies for IL-4. Int Arch Allergy Immunol 113: 61–64PubMedGoogle Scholar
  26. 26.
    Cooke RA, Vander Veer A (1916) Human sensitisation. J Immunol 1: 201–305Google Scholar
  27. 27.
    Ruiz RGG, Richards D, Kemeny DM et al (1991) Neonatal IgE: A poor screen for atopic disease. Clin Exp Allergy 21: 467–472PubMedGoogle Scholar
  28. 28.
    D’Andrea A, Aste-Amezaga M, Valianta NM et al (1993) IL-10 inhibits human lymphocyte IFNγ production by suppressing natural killer cell stimulatory factor/IL-12 synthesis in accessory cells. J Exp Med 178: 1041–1048PubMedGoogle Scholar
  29. 29.
    Warner J, Jones AC, Miles EA et al (1997) Prenatal origins of allergy and asthma. The rising trends in asthma. Ciba Foundation Symposium 206: 220–232PubMedGoogle Scholar
  30. 30.
    Warner JA, Miles EA, Jones AC et al (1994) Is deficiency of interferon gamma production by allergen triggered blood cells a predictor of atopic eczema. Clin Exp Allergy 24: 423–430PubMedGoogle Scholar
  31. 31.
    Nicod LP (1996) Role of antigen-presenting cells in lung immunity. Eur Respir Rev 6: 142–150Google Scholar
  32. 32.
    Sporik R, Holgate ST, Platts-Mills TAE et al (1990) Exposure to house dust mite allergen (Der P1) and the development of allergy in childhood: A prospective study. N Eng J Med 323: 502–507Google Scholar
  33. 33.
    Warner JA, Jones AC, Miles EA et al (1996) Materno-fetal interaction and allergy. Allergy 51: 447–451PubMedGoogle Scholar
  34. 34.
    Azzawi M, Johnston PW, Majumdar S et al (1992) T lymphocytes and activated eosinophils in asthma and cystic fibrosis. Am Rev Respir Dis 145: 1477–1482PubMedGoogle Scholar
  35. 35.
    Kay AB (1996) Pathology of mild, severe and fatal asthma. Am J Respir Crit Care Med 154: S66–S69PubMedGoogle Scholar
  36. 36.
    Sur S, Crotty TB, Kephart GM et al (1993) Sudden onset fatal asthma — A distinct entity with few eosinophils and relatively more neutrophils in the airway submucosa? Am Rev Respir Dis 148: 713–719PubMedGoogle Scholar
  37. 37.
    Koshino T, Arai Y Miyamoto Y et al (1996) Airway basophil and mast cell density in patients with bronchial asthma relationship to bronchial hyperresponsiveness. J Asthma 33(2): 89–95PubMedGoogle Scholar
  38. 38.
    Linsley PS, Ledbetter JA (1993) The role of CD28 receptor during T cell responses to antigen. Annu Rev Immunol 11: 191–212PubMedGoogle Scholar
  39. 39.
    Holt PG (1996) Current concepts in pulmonary immunology: regulation of primary and secondary responses to inhaled antigen. Eur Respir Rev 6(36): 128–135Google Scholar
  40. 40.
    Semper AE, Hartley JA (1996) Dendritic cells in the lung-what is their relevance to asthma. Clin Exp Allergy 26(5): 485–490PubMedGoogle Scholar
  41. 41.
    Moller GM, Overbeek SE, Van-HeldenMeeuwsen CG et al (1996) Increased numbers of dendritic cells in the bronchial mucosa of atopic asthmatic patients: downregulation by inhaled corticosteroids. Clin Exp Allergy 26(5): 517–524PubMedGoogle Scholar
  42. 42.
    Holt PG (1986) Downregulation of immune responses in the lower respiratory tract: The role of alveolar macrophages. Clin Exp Immunol 63: 261–270PubMedGoogle Scholar
  43. 43.
    Sousa AR, Trigg CJ, Lane SJ et al (1997) Effect of inhaled glucocorticosteroids on IL-1β and IL-1 receptor antagonist (IL-lra) expression in asthmatic bronchial epithelium. Thorax 52: 407–410PubMedGoogle Scholar
  44. 44.
    Aubas P, Cosso B, Godard P et al (1984) Decreased suppressor cell activity of alveolar macrophages in bronchial asthma. Am Rev Respir Dis 130: 875–878PubMedGoogle Scholar
  45. 45.
    Gosset P, Lassalle P, Tonnel AB et al (1988) Production of an interleukin 1 inhibitory factor by human alveolar macrophages from normals and allergic asthmatic patients. Am Rev Respir Dis 138: 40–46PubMedGoogle Scholar
  46. 46.
    Metzger ZWI, Hoffeld JT, Oppenheim JJ (1980) Macrophage mediated suppression. J Immunol 124: 983–988PubMedGoogle Scholar
  47. 47.
    Lyons CR, Ball EJ, Toews GB et al (1986) Inability of human alveolar macrophages to stimulate resting T-cells correlates with decreased antigen-specific T-cell macrophage binding. J Immunol 137: 1173–1180PubMedGoogle Scholar
  48. 48.
    Van Kooyk Y, Van de Wiel-Van Kemenade P et al (1989) Enhancement of LFA-1 mediated cell adhesion by triggering through CD2 or CD3 on T-lymphocytes. Nature 342: 811–813PubMedGoogle Scholar
  49. 49.
    Chelen CJ, Fang Y, Freeman GJ et al (1995) Human alveolar antigens present antigen ineffectively due to defective expression of B-7 co-stimulatory cell surface molecules. J Clin Invest 95: 1415–1421PubMedGoogle Scholar
  50. 50.
    Agea E, Spinozzi F et al (1998) Expression of B7 costimulatory molecules and CD1a antigen by alveolar macrophages in bronchial asthma. Clin Exp Allergy 28: 1359–1367PubMedGoogle Scholar
  51. 51.
    van Gool S, Vandenberghe P, De Boer M, Ceuppens JL (1996) CD80, CD86 and CD40 provide accessory signals in a multiple-step T-cell activation model. Immunol Rev 153: 111: 129–155Google Scholar
  52. 52.
    Bluestone JA (1997) Is CTLA-4 a master switch for peripheral T cell tolerance? J Immunol 58: 1989–1993Google Scholar
  53. 53.
    Krummel MF, Allison JP (1995) CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 182: 459–465PubMedGoogle Scholar
  54. 54.
    Klinzman SJ, DeSanctis GT, Cemades M et al (1996) Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model. J Clin Invest 98: 2693–2699Google Scholar
  55. 55.
    Wu Y, Guo Y, Huang A et al (1997) CTLA-4-B-7 interaction is sufficient to costimulate T cell clonal expansion. J Exp Med 185(7): 1327–1335PubMedGoogle Scholar
  56. 56.
    Liu Y (1997) Is CTLA-4 a negative regulator for T cell activation? Immunology Today 18(12): 569–572PubMedGoogle Scholar
  57. 57.
    Lenschow DJ, Walunas TL, Bluestone JA (1996) CD28/B7 system of cell costimulation. Annu Rev Immunol 14: 233–258PubMedGoogle Scholar
  58. 58.
    Tsuyuki S, Tsuyuki J, Einsle K et al (1997) Co-stimulation through B7-2(CD86) is required for the induction of a lung mucosal T helper cell 2(TH2)immune response and altered airway hyperresponsiveness. J Exp Med 185(9): 1671–1679PubMedGoogle Scholar
  59. 59.
    Keane-Myers A, Gause WC, Linsley PS et al (1997) B7-CD28/CTLA4 costimulatory pathways are required for the development of T helper cell 2-mediated allergic airway responses to inhaled antigens. J Immunol 158: 2042–2049PubMedGoogle Scholar
  60. 60.
    Keane-Myers A, Gause WC, Finkelman FD et al (1998) Development of murine allergic asthma is dependent upon B7-2 costimulation. J Immunol 160: 1036–1043PubMedGoogle Scholar
  61. 61.
    van Neerven RJ, van de Pol MM, van der Zee JS et al (1998) Inhibition of allergen-specific proliferation and cytokine production of human T lymphocytes by blocking the CD28-CD86 costimulatory pathway. Clin Exp Allergy 28(7): 808–816PubMedGoogle Scholar
  62. 62.
    Jaffer Z, Roberts K, Pandit A et al (1997) B7 costimulation is required for IL-5 and IL-13 expression by T cells resident in bronchial biopsy tissue of asthmatics after allergen stimulation. Immunology 92(S1): 45–A12.15Google Scholar
  63. 63.
    Lebwohl MJ, Kang S, Guzzo C et al (1997) CTLA4-Ig (BMS-188667)-mediated blockade of T cell co-stimulation in patients with psoriasis vulgaris. J Inv Dermatology 108: 570, A198Google Scholar
  64. 64.
    Cees van Cooten, Banchereau J (1997) Functions of CD40 on B cells, dendritic cells and other cells. Current Opinions in Immunology 9: 330–337Google Scholar
  65. 65.
    Boussiotis VA, Freeman GJ, Gribben JG, Nadler LM (1996) The role of B7-1/B7-2: CD28/CTLA4 pathways in the prevention of anergy, induction of productive immunity and downregulation of the immune response. Immunological Reviews 153: 5–25PubMedGoogle Scholar
  66. 66.
    Maurer D, Ebner C, Reininger B et al (1995) The high affinity IgE receptor (Fcε;RI) mediates IgE-dependent allergen presentation. J Immunol 154: 6285–6290PubMedGoogle Scholar
  67. 67.
    Tunon-de-lara JM, Redington AE, Bradding P, Holgate ST et al (1996) Dendritic cells in normal and asthmatic airways: expression of the alpha subunit of the high affinity IgE receptor (FcERI-a). Clin Exp Allergy 26: 648–655PubMedGoogle Scholar
  68. 68.
    Barnes PJ, Karin M (1997) Nuclear factor-KB — A pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336(15): 1066–1071PubMedGoogle Scholar
  69. 69.
    Muegge K, Durum SK (1990) Cytokines and transcription factors. Cytokine 2: 1–8PubMedGoogle Scholar
  70. 70.
    Adcock IM, Gelder CM, Shirasaki H et al (1992) Effects of steroids on transcription factors in human lung. Am Rev Respir Dis 145: A834Google Scholar
  71. 71.
    Barnes PJ, Adcock IM (1995) Transcription factors. Clin Exp Allergy 25(S2): 46–49PubMedGoogle Scholar
  72. 72.
    Salvi SS, Semper AE, Papi A et al (1998) Human lung epithelial cells express IL-5 mRNA. J Allergy Clin Immunol 101(1): S19Google Scholar
  73. 73.
    Romagniani S (1990) Regulation and deregulation of human IgE synthesis. Immunol Today 11: 316–321Google Scholar
  74. 74.
    Schleimer RP, Sterbinsky CA, Kaiser CA et al (1992) Interleukin 4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium: association with expression of VCAM-1. J Immunology 148: 1086–1092Google Scholar
  75. 75.
    Walsh GM, Mermod JJ, Hartneil A et al (1991) Human eosinophil, but not neutrophil, adherence to IL-1 stimulated HWEC is α4β1 (VLA-4) dependent. J Immunol 146: 3419PubMedGoogle Scholar
  76. 76.
    Pretolani M, Goldman M (1997) IL-10: A potential therapy for allergic inflammation Immunol Today 277-280Google Scholar
  77. 77.
    Naseer T, Minshall EM, Leung DYM et al (1997) Expression of IL-12 and IL-13 mRNA in asthma and their modulation in response to steroid therapy. Am J Respir Crit Care Med 155: 845–851PubMedGoogle Scholar
  78. 78.
    Robinson DS, Hamid Q, Ying S et al (1992) Predominant Th2-type bronchoalveolar lavage T lymphocyte population in atopic asthma. N Eng J Med 326: 298–304Google Scholar
  79. 79.
    Del Prete G, de Carli M, Almerigogna F et al (1993) Human IL-10 is produced by Thl and Th2 T cell clones and inhibits their antigen specific proliferation and cytokine production. J Immunol 150: 353–360PubMedGoogle Scholar
  80. 80.
    Robinson DS, Tsicopoulos A, Meng Q et al (1996) Increased IL-10 mRNA expression in atopic allergy and asthma. Am J Respir Cell Mol Biol 14: 113–117PubMedGoogle Scholar
  81. 81.
    Hseih CS, Macatonia SE, Tripp CS et al (1993) Development of Thl CD4+ T cells through IL-12 produced by Listeria induced macrophages. Science 260: 547–549Google Scholar
  82. 82.
    Manetti R, Parronchi P, Guidizi MG et al (1993) Natural killer stimulatory factor (IL-12) induces Th1-specific immune responses and inhibits the development of IL-4 producing Th cells. J Exp Med 177: 1199–1204PubMedGoogle Scholar
  83. 83.
    Gavett SH, O’Hearn DJ, Li Z et al (1995) Interleukin-12 inhibits antigen-induced airway hyperresponsiveness, inflammation and Th2 cytokine expression in mice. J Exp Med 182(5): 1527–1536PubMedGoogle Scholar
  84. 84.
    Defrance T, Carayon P, Billian G et al (1994) Interleukin 13 is a B-cell stimulating factor. J Exp Med 179: 135–143PubMedGoogle Scholar
  85. 85.
    Kroegel C, Julius P, Matthys H et al (1996) Endobronchial secretion of IL-13 following local allergen challenge in atopic asthma: relationship to IL-4 and eosinophil counts. Eur Respir J 9: 899–904PubMedGoogle Scholar
  86. 86.
    Humbert M, Durham SR, Kimmitt P et al (1997) Elevated expression of mRNA encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma. J Allergy Clin Immunol 99: 657–665PubMedGoogle Scholar
  87. 87.
    Bochner BS, Klunk DA, Sterbinsky SA et al (1995) IL-13 selectively induces vascular cell adhesion molecule-lexpression in human endothelial cells. J Immunol 154: 799–803PubMedGoogle Scholar
  88. 88.
    Shau-Ku Huang, Hui-Qing Xiao, Jorg Kleine-Tebbe et al (1995) IL-13 expression at the sites of allergen challenge in patients with asthma. J Immunol 155: 2688–2694PubMedGoogle Scholar
  89. 89.
    Cruikshank WW, Long A, Tarpy RE et al (1995) Early identification of IL-16 (Lymphocyte chemoattractant factor) and macrophage inflammatory protein 1α(MIP1α) in BALF of antigen-challenged asthmatics. Am J Respir Cell Mol Biol 13: 738–747PubMedGoogle Scholar
  90. 90.
    Cruikshank WW, Berman JS, Theodore AC et al (1987) Lymphokine activation of T4+ lymphocytes and monocytes. J Immunol 138: 3817–3825PubMedGoogle Scholar
  91. 91.
    Laberge S, Ernest P, Ghaffar O et al (1997) Increased expression of IL-16 in bronchial mucosa of subjects with atopic asthma. Am J Respir Cell Mol Biol 17(2): 193–202PubMedGoogle Scholar
  92. 92.
    Bellini A, Yoshimura H, Vitori E et al (1993) Bronchial epithelial cells of patients with asthma release chemoattractant factors for T lymphocytes. J Allerg Clin Immunol 92: 412–424Google Scholar
  93. 93.
    Okamura H, Tsutsui H, Komatsu T et al (1995) Nature 378: 88–91PubMedGoogle Scholar
  94. 94.
    Yoshimoto T, Okamura H, Tagawa Y et al (1997) Interleukin 18 togethor with interleukin 12 inhibits IgE production by induction of IFNy production from activated B cells. Proc Natl Acad Sci USA 94(8): 3948–3953PubMedGoogle Scholar
  95. 95.
    Bradding P (1996) Human mast cell cytokines. Clin Exp Allergy 26: 13–19PubMedGoogle Scholar
  96. 96.
    Bradding P, Roberts JA, Britten KM et al (1994) Interleukin-4,-5, and-6 and tumor necrosis factor-α in normal and asthmatic airways: Evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol 10: 471–480PubMedGoogle Scholar
  97. 97.
    Andersson U, Matsuda T (1989) Human interleukin 6 and tumor necrosis factor-α production studied at a single cell level. Eur J Immunol 19: 1157–1160PubMedGoogle Scholar
  98. 98.
    Broide DH, Lotz M, Cuomo AJ et al (1992) Cytokines in symptomatic asthma airways. J Allerg Clin Immunol 89: 958–967Google Scholar
  99. 99.
    Kips JC, Tavernier J, Pauwels RA (1992) Tumor necrosis factor (TNF) causes bronchial hyperresponsiveness in rats. Am Rev Respir Dis 145: 2–336Google Scholar
  100. 100.
    Ming WJ, Bersani L, Mantovani A (1987) Tumor necrosis factor is chemotactic for monocytes and polymorphonuclear leucocytes. Immunol 138: 1469–1474Google Scholar
  101. 101.
    Silberstein DS, Davis jR (1986) Tumor necrosis factor enhances eosinophil toxicity to Schistosoma Mansoni larvae. Proc Natl Acad Sci USA 83: 1055–1059PubMedGoogle Scholar
  102. 102.
    Slungaard A, Vercellotte GM, Walker G et al (1990) Tumor necrosis factor/cachectin stimulates eosinophil oxidant production and toxicity towards human endothelium. J Exp Med 171: 2025–2031PubMedGoogle Scholar
  103. 103.
    Bevilacqua MP, Stengelin S, Gimbrone MA et al (1989) Endothelial leucocyte adhesion molecule-1: An inducible receptor for neutrophils related to complement regulatory proteins and lectins. Science 243: 1160–1165PubMedGoogle Scholar
  104. 104.
    Osborn L, Hession R, Tizard R et al (1989) Direct expression and cloning of vascular cell adhesion molecule-1, a cytokine-endothelial protein that binds to lymphocytes. Cell 59: 1203–1211PubMedGoogle Scholar
  105. 105.
    Pober JS, Gimbrone MA, Lapierre LA et al (1986) Overlapping pattern of activation of human endothelial cells by interleukin 1, Tumor necrosis factor, and immune interferon. Immunol 137: 1893–1896Google Scholar
  106. 106.
    Shah A, Church MK, Holgate ST (1995) Tumor necrosis factor-α: a potential mediator of asthma. Clin Exp Allergy 25: 1038–1044PubMedGoogle Scholar
  107. 107.
    Corrigan CJ, Hartnell A, Kay AB (1988) T lymphocyte activation in acute severe asthma. Lancet I: 1129–1132Google Scholar
  108. 108.
    Azzawi M, Bradley B, Jeffery PK et al (1990) Identification of activated T lymphocytes and eosinophils in bronchial biopsies in stable atopic asthmatics. Am Rev Respir Dis 142: 1407–1413PubMedGoogle Scholar
  109. 109.
    Hamid Q, Barkans J, Robinson DS et al (1992) Co-expression of CD25 and CD3 in atopic allergy and asthma. Immunol 75: 659–663Google Scholar
  110. 110.
    Robinson DS, Bentley AM, Hartnell A et al (1993) Activated memory T helper cells in bronchoalveolar lavage from atopic asthmatics. Relationship to asthma symptoms, lung function and bronchial responsiveness. Thorax 48: 26–32PubMedGoogle Scholar
  111. 111.
    Ying S, Durham SR, Corrigan CJ et al (1995) Phenotype of cells expressing mRNA for Th2-type (IL-4 and IL-5) and Th1-type (IL-2 and interferon gamma) cytokines in bronchoalveolar lavage and bronchial biopsies from atopic asthmatics and normal control subjects. Am J Respir Cell Mol Biol 12: 477–487PubMedGoogle Scholar
  112. 112.
    Humbert M, Durham SR, Ying S et al (1996) IL-4 and IL-5 mRNA and protein in bronchial biopsies from atopic and non-atopic asthmatics: evidence against intrinsic asthma being a distinct immunopathological entity. Am J Respir Crit Care Med 154: 1497–1504PubMedGoogle Scholar
  113. 113.
    Center DM, Kornfeld H, Cruikshank W (1996) Interleukin 16 and its function as a CD4 ligand. Immunol Today 476-481Google Scholar
  114. 114.
    Gause WC, Mitro V, Via C et al (1997) Do effector and memory T helper cells also need B7 ligand costimulatory signals? J Immunol 159: 1055–1058PubMedGoogle Scholar
  115. 115.
    Corrigan CJ, Hamid Q, North J et al (1995) Peripheral blood CD4 but not CD8 T-lymphocytes in patients with exacerbation of asthma transcribe and translate mRNA encoding cytokines which prolong eosinop~hil survival in the context of a Th2-type pattern: effect of glucocorticosteroid therapy. Am J Respir Cell Mol Biol 12: 567–578PubMedGoogle Scholar
  116. 116.
    Hamid Q, Azzawi M, Ying S et al (1991) Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthmatics. J Clin Invest 87: 1541–1546PubMedGoogle Scholar
  117. 117.
    Robinson DS, Hamid Q, Ying S (1993) Prednisolone treatment in asthma is associated with modulation of broncho-alveolar lavage cell IL-4, IL-5 and interferon-γ cytokine gene expression. Am Rev Respir Dis 148: 401–406PubMedGoogle Scholar
  118. 118.
    Bentley AM, Hamid Q, Robinson DS et al (1996) Prednisolone treatment in asthma. Reduction in the number of eosinophils, T-cells, tryptase-only positive mast cells, and modulation of IL-4, IL-5 and interferon gamma cytokine gene expression within the bronchial mucosa. Am J Respir Crit Care Med 153: 551–556PubMedGoogle Scholar
  119. 119.
    Robinson DS, Ying S, Bentley AM et al (1993) Relationship among numbers of bron-choalveolar lavage cells expressing mRNA for cytokines, asthma symptoms and airway methacholine responsiveness in atopic asthma. Allergy Clin Immunol 92: 397–403Google Scholar
  120. 120.
    Kay AB (1997) T cells as orchestrators of the asthmatic response. The rising trends in asthma. Ciba Foundation Symposium 206: 56–70PubMedGoogle Scholar
  121. 121.
    Sun Ying, Humbert M, Barkans J et al (1997) Expression of IL-4 and IL-5 mRNA and protein product by CD4+ and CD8+ T-cells, eosinophils and mast cells in bronchial biopsies obtained from atopic and non-atopic asthmatics. J Immunol 158: 3539–3544Google Scholar
  122. 122.
    Leung DYM, Martin RJ, Szefler SJ et al (1995) Dysregulation of IL-4, IL-5 and IFNγ gene expression in steroid-resistant asthma. J Exp Med 181: 33–40PubMedGoogle Scholar
  123. 123.
    Sher E, Leung DYM, Surs W et al (1994) Steroid resistant asthma. Cellular mechanisms contributing to inadequate response to glucocorticosteroid therapy. J Clin Invest 93: 33–39PubMedGoogle Scholar
  124. 124.
    Szefler SJ, Leung DYM (1997) Glucorticoid-resistant asthma: pathogenesis and clinical implications for management. Eur Respir J 10: 1640–1647PubMedGoogle Scholar
  125. 125.
    Lane SJ, Lee TH (1997) Mechanisms and detection of glucocorticoid insensitivity in asthma. ACI International 9/6Google Scholar
  126. 126.
    Adcock IM, Lane SJ, Brown CR et al (1995) Abnormal glucocorticosteroid receptor-activator protein 1 interaction in steroid resistant asthma. J Exp Med 182: 1951–1958PubMedGoogle Scholar
  127. 127.
    Alexander AG, Barnes NC, Kay AB (1992) Trial of cyclosporin A in corticosteroid-dependent chronic severe asthma. Lancet 339: 324–328PubMedGoogle Scholar
  128. 128.
    Lock SH, Kay AB, Barnes NC (1996) Double-blind placebo-controlled study of cyclosporin A as a corticosteroid-sparing agent in corticosteroid-dependant asthma. Am J Respir Crit Care Med 153: 509–514PubMedGoogle Scholar
  129. 129.
    Sihra BS, Durham SR, Walker S et al (1997) Effect of Cyclosporin A on the allergen-induced late asthmatic response. Thorax 52: 447–452PubMedGoogle Scholar
  130. 130.
    Kay AB, Frew AJ, Corrigan CJ et al (1998) The T cell hypothesis of chronic asthma. In: AB Kay (ed): Allergy and allergic diseases. Blackwell Science, OxfordGoogle Scholar
  131. 131.
    Teran LM, Carroll M, Frew AJ (1996) Leucocyte recruitment after local endobronchial allergy challenge in asthma: relationship to procedure and to airway IL-8 release. Am J Respir Crit Care Med 154: 469–476PubMedGoogle Scholar
  132. 132.
    Holgate ST (1993) Mediators and cytokine mechanisms in asthma. Altyounan address. Thorax 48: 103–109PubMedGoogle Scholar
  133. 133.
    Louis R, Shute J, Biagi S et al (1997) Cell infiltration, ICAM-1 expression, and eosinophil chemotactic activity in asthmatic sputum. Am J Respir Crit Care Med 155: 466–472PubMedGoogle Scholar
  134. 134.
    Weiler PF (1997) Updates on cells and cytokines. Human eosinophils. J Allergy Clin Immunol 100: 283–287Google Scholar
  135. 135.
    Moqbel R, Ying S, Barkans J et al (1995) Identification of mRNA for IL-4 in human eosinophils with granule localisation and release of the translated product. J Immunol 155(10): 4939–4947PubMedGoogle Scholar
  136. 136.
    Makker HK, Holgate ST (1994) Mechanisms of exercise-induced asthma. Eur J Clin Inv 24: 571–585Google Scholar
  137. 137.
    Bradding P, Feather IH, Wilson S et al (1993) Immunolocalisation of cytokines in the nasal mucosa of normal and perennial rhinitic subiects: the mast cell as a source of IL-4, IL-5 and IL-6 in human allergic mucosal inflammation. J Immunol 151: 3853–3865PubMedGoogle Scholar
  138. 138.
    Okayama Y, Lau LC-K, Church MK (1996) TNFα production by human lung mast cells in response to stimulation by stem cell factor and FcER1 cross-linkage. J Immunol; in press Google Scholar
  139. 139.
    Montefort S, Gratziou C, Goulding D (1994) Bronchial biopsy evidence for leucocyte infiltration and upregulation of leucocyte endothelial cell adhesion molecules 6 hours after local allergen challenge of sensitised asthmatic airway. J Clin Inv 93: 1411–1421Google Scholar
  140. 140.
    Campbell AM (1997) Bronchial epithelial cells in asthma. Allergy 52: 483–489PubMedGoogle Scholar
  141. 141.
    Devalia JL, Campbell AM, Sapeford RJ et al (1993) Effects of nitrogen dioxide on synthesis of inflammatory cytokines expressed by human bronchial epithelial cells in vitro. Am J Respir Cell Mol Biol 9: 271–278PubMedGoogle Scholar
  142. 142.
    Vignola AM, Campbell AM, Chanez P et al (1993) Activation by histamine of bronchial epithelial cells from nonasthmatic subjects. Am J Respir Cell Mol Biol 9: 411–417PubMedGoogle Scholar
  143. 143.
    Altman LC, Ayars GH, Baker C et al (1993) Cytokines and eosinophil-derived cationic proteins upregulate ICAM-1 on human nasal epithelial cells. J Allergy Clin Immunol 92: 527PubMedGoogle Scholar
  144. 144.
    Souques F, Crampette L, Mondain M et al (1995) Stimulation of dispersed nasal polyp cells by hyperosmolar solutions. J Allergy Clin Immunol 96: 980–985PubMedGoogle Scholar
  145. 145.
    Kalinski P, Hilkens CMU, Snijders A et al (1997) IL-12 deficient dendritic cells, generated in the presence of PGE2 promote type 2 cytokine production in maturing human naive T helper cells. J Immunol 159: 28–35PubMedGoogle Scholar
  146. 146.
    Campbell AM, Vignola AM, Chanez P et al (1994) Low affinity receptors for IgE on human bronchial epithelial cells. Immunol 82: 506–508Google Scholar
  147. 147.
    Marini M, Vittori E, Hollemborg J et al (1992) Expression of the potent inflammatory cytokines, GM-CSF and IL-6 and IL-8, in bronchial epithelial cells of patients with asthma. J Allergy Clin Immunol 89: 1001–1009PubMedGoogle Scholar
  148. 148.
    Cromwell O, Hamid Q, Corrigan CJ et al (1992) Expression and generation of IL-8, IL-6 and GM-CSF by bronchial epithelial cells and enhancement by IL-1β and TNFα. Immunol 77: 330–337Google Scholar
  149. 149.
    Wang DH, Devalia JL, Xia C et al (1996) Expression of RANTES by human bronchial epithelial cells in vitro and in vivo and the effect of corticosteroids. Am J Respir Cell Mol Biol 14: 27–35PubMedGoogle Scholar
  150. 150.
    Barnes PJ (1997) NFκB. N Engl J Med 336: 1066–1071PubMedGoogle Scholar
  151. 151.
    Asano K, Nakamura H, Lilly CM et al (1997) IFNy induces prostaglandin GIH synthase-2 through an autocrine loop via the epidermal growth factor receptor in human bronchial epithelial cells. J Clin Inv 99: 1057–1063Google Scholar
  152. 151.
    Shibata Y, Nakamura H, Kato S et al (1996) Cellular detachment and deformation induce IL-8 gene expression in human bronchial epithelial cells. J Immunol 156: 772–777PubMedGoogle Scholar
  153. 152.
    Wilson SJ, Leone BA, Anderson D, Manning A, Holgate ST (1999) Immunohistochemical analysis of the activation of NF-κB and expression of associated cytokines and adhesion molecules in human models of allergic inflammation. J Pathology; submitted for publication Google Scholar
  154. 153.
    Manolitsas ND, Trigg CJ, McAulay AE et al (1994) The expression of intercellular adhesion molecule-1 and the β1-integrins in asthma. Eur Respir J 7: 1439–1444PubMedGoogle Scholar
  155. 154.
    Corne J, Holgate ST (1997) Mechanisms of virus induced exacerbations of asthma. Thorax 52: 380–389PubMedGoogle Scholar
  156. 155.
    Vignola AM, Merendino AM, Chiapparo G et al (1999) Heterogeneous effects of TGFβ, EGF, IL-4 and IL-5 on ICAM-1 and α3β1 expression on fibronectin release by human pulmonary epithelial cells. Thorax; in press Google Scholar
  157. 156.
    Alving K, Weitzberg E, Lundberg JM (1993) Increased amounts of nitric oxide in exhaled air. Eur Resp J 6: 1268–1270Google Scholar
  158. 157.
    Kharitonov SA, Yates D, Robbins RA, Logan-Sinclair R et al (1994) Increased nitric oxide in exhaled air of asthmatic patients. Lancet 343: 133–135PubMedGoogle Scholar
  159. 158.
    Nijkamp FP, Folkerts G (1997) Nitric oxide: Initiator and modulator. Clin Exp Allergy 27: 347–350PubMedGoogle Scholar
  160. 159.
    Holgate ST (1996) The inflammation-repair cycle in asthma: possible new biomarkers of disease activity. Eur Respir Rev 6: 4–10Google Scholar
  161. 160.
    Barnes PJ (1995) Nitric oxide and airway disease. Ann Int Med 27: 91–97Google Scholar
  162. 161.
    Redington AE, Springall DR, Holgate S et al (1997) Airway endothelin levels in asthma: influence of allergen challenge and maintenance corticosteroid therapy. Eur Resp J 10: 1026–1032Google Scholar
  163. 162.
    Mattoli S, Mezzetti M, Riva G et al (1990) Specific binding of endothelin on human bronchial smooth muscle cells in culture and secretion of endothelin-like material from bronchial epithelial cells. Am J Resp Cell Mol Biol 3: 145–151Google Scholar
  164. 163.
    Yanagisawa M, Kurihara H, Kimura S et al (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332: 411–415PubMedGoogle Scholar
  165. 164.
    Springall DR, Howarth PH, Counihan H et al (1991) Endothelin immunoreactivity of airway epithelium in asthmatic patients. Lancet 337: 697–701PubMedGoogle Scholar
  166. 165.
    Redington AE, Springall DR, Ghatei MA et al (1995) Endothelin in BALF and its relationship to airflow obstruction in asthma. Am Rev Resp Crit Care Med 151: 1034–1039Google Scholar
  167. 166.
    Newton R, Kuitert LM, Slater DM et al (1997) Cytokine induction of cytosolic phospholipase A2 and cyclooxygenase-2 mRNA is suppressed by glucocorticosteroids in human epithelial cells. Life Science 60: 67–78Google Scholar
  168. 167.
    Sousa A, Trigg CJ, Lane SJ et al (1997) Effect of inhaled glucocorticosteroids on IL-1β and IL-1ra expression in asthmatic bronchial epithelium. Thorax 52: 407–410PubMedGoogle Scholar
  169. 168.
    Wilson S, Wallin A, Sandstrom T et al (1997) Effects of budesonide treatment on expression of NF-κB and NF-κB regulated cytokines and adhesion molecules in bronchial mucosa of mild asthmatics. Am J Respir Crit Care Med 155(2): A698Google Scholar
  170. 169.
    Brown PJ, Greville HW, Finucane KE (1980) Asthma and irreversible airflow obstruction. Thorax 35: 298–302Google Scholar
  171. 170.
    Huber HL, Koessler KK (1922) The pathology of bronchial asthma. Arch Int Med 30: 689–760Google Scholar
  172. 171.
    Ebina M, Takahashi T, Chiba T et al (1993) Cellular hypertrophy and hyperplasia of airway smooth muscles underlying bronchial asthma: a 3-D morphometric study. Am Rev Resp Dis 148: 720–726PubMedGoogle Scholar
  173. 172.
    Takizawa T, Thurlbeck WM (1971) Muscle and mucus gland size in the major bronchi of patients with chronic bronchitis, asthma and asthmatic bronchitis. Am Rev Resp Dis 104: 331–336PubMedGoogle Scholar
  174. 173.
    Li X, Wilson JW (1997) Increased vascularity of the bronchial mucosa in mild asthma. Am J Respir Crit Care Med 156: 229–233PubMedGoogle Scholar
  175. 174.
    Hirst SJ (1996) Airway smooth muscle cell culture: Application to studies of airway wall remodelling and phenotype plasticity in asthma. Eur Respir J 9: 808–820PubMedGoogle Scholar
  176. 175.
    Lynch DA, Newell JD, Tschomper BA et al (1993) Uncomplicated asthma in adults: comparison of CT appearances of the lungs in asthmatic and healthy subjects. Radiology 188: 829–833PubMedGoogle Scholar
  177. 176.
    Paganin F, Seneterre E, Chanez P et al (1996) Computerised tomography of the lungs in asthma: influence of disease severity and aetiology. Am J Respir Crit Care Med 153: 110–114PubMedGoogle Scholar
  178. 177.
    Roche WR, Beasley R, Williams JH et al (1989) Subepithelial fibrosis in the bronchi of asthmatics. Lancet i: 520–524Google Scholar
  179. 178.
    Brewster CEP, Howarth PH, Djukanovic R et al (1990) Myofibroblasts and subepithelial fibrosis in bronchial asthma. Am J Respir Cell Mol Biol 3: 507–511PubMedGoogle Scholar
  180. 179.
    Wilson JW, Li X (1997) The measurement of reticular basement membrane and submucosal collagen in the asthmatic airway. Clin Exp Allergy 27: 363–371PubMedGoogle Scholar
  181. 180.
    Redington AE, Howarth PH (1997) Airway wall remodelling in asthma. Thorax 52: 310–312PubMedGoogle Scholar
  182. 181.
    Redington AE, Madden J, Frew AJ et al (1997) Transforming growth factor β1 in asthma-measurement in bronchoalveolar lavage fluid. Am J Respir Crit Care Med 156: 642–647PubMedGoogle Scholar
  183. 182.
    Anwar AR, Moqbel R, Walsh GM et al (1993) Adhesion to fibroneetin prolongs eosinophil survival. J Exp Med 177: 839–843PubMedGoogle Scholar
  184. 183.
    Georas SN, McIntyre WB, Ebisawa M (1993) Expression of a functional laminin receptor a6bl (VLA-6) on human eosinophil. Blood 82: 2872–2879PubMedGoogle Scholar
  185. 184.
    Goldring K, Warner JA (1997) Cell matrix interactions in asthma. Clin Exp Allergy 27: 22–27PubMedGoogle Scholar
  186. 185.
    Minshall EM, Leung DYM, Martin RJ et al (1997) Eosinophil-associated TGF-β1 mRNA expression and airways fibrosis in bronchial asthma. Am J Respir Cell Mol Biol 17: 326–333PubMedGoogle Scholar
  187. 186.
    Shute J, Parmar J, Holgate ST (1997) Urinary glyeosaminoglyean levels are increased in acute severe asthma — a role for eosinophil-derived gelatinase B? Int Arch Allergy Immunol 113: 366–367PubMedGoogle Scholar
  188. 187.
    Ruoss SJ, Hartmann T, Caughey GH (1991) Mast cell tryptase is a mitogen for cultured fibroblasts. J Clin Inv 88: 493–499Google Scholar
  189. 188.
    Cutz E, Levison H, Cooper DM (1978) Ultrastructure of airways in children with asthma. Histopathology 2: 407–421PubMedGoogle Scholar
  190. 189.
    Djukanovic R, Wilson JW, Britten KM et al (1992) Effect of inhaled corticosteroids on airway inflammation and symptoms in asthma. Am Rev Respir Dis 145: 669–674PubMedGoogle Scholar
  191. 190.
    Laitinen LA, Laitinen A (1996) Remodelling of asthmatic airways by glucocorticosteroids. J Allergy Clin Immunol 97: 153–158PubMedGoogle Scholar
  192. 191.
    Djukanovic R, Howarth PH, Vrugt B et al (1995) Determinants of asthma severity. Int Arch Allergy Immunol 107: 389PubMedGoogle Scholar
  193. 192.
    Walker, C, Kaegi MK, Braun P et al (1991) Activated T cells and eosinophilia in bronchoalveolar lavages from subjects with asthma correlated with disease severity. J Allergy Clin Immunol 88: 935–942PubMedGoogle Scholar
  194. 193.
    Sont JK, Han J, van Krieken JM et al (1996) Relationship between the inflammatory infiltrate in bronchial biopsy specimens and clinical severity of asthma in patients treated with inhaled steroids. Thorax 51: 496–502PubMedGoogle Scholar
  195. 194.
    Bradley BL, Azzawi M, Jacobson M et al (1991). Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness. J Allergy Clin Immunol 889: 661–674Google Scholar
  196. 195.
    Sur S, Crotty TB, Kephart GM et al (1993) Sudden onset fatal asthma — A distinct entity with few eosinophils and relatively more neutrophils in the airway submueosa? Am Rev Respir Dis 148: 713–719PubMedGoogle Scholar
  197. 196.
    Fahy JV, Kim KW, Liu J et al (1995) Respiratory pathophysiological responses-prominent neutrophilic inflammation in sputum from subjects with asthma exacerbations. J Allergy Clin Immunol 95(4): 843–852PubMedGoogle Scholar
  198. 197.
    Wenzel SE, Szefler SJ, Leung DYM et al (1997) Bronchoscopic evaluation of severe asthma, persistent inflammation associated with high dose glucocorticosteroids. Am J Respir Crit Care Med 156: 737–743PubMedGoogle Scholar
  199. 198.
    Cox G (1995) Glucocorticosteroid treatment inhibits apoptosis in human neutrophils. J Immunol 154: 4719–4725PubMedGoogle Scholar
  200. 199.
    Chanez P, Paradis A, Vignola M et al (1996) Changes in bronchial epithelium of steroid (GCs) dependent asthmatics. Am J Respir Crit Care Med 153: 212Google Scholar
  201. 200.
    Weiss KB, Gergen PJ, Hodgson TA (1992) An economic evaluation of asthma in the United States. N Engl J Med 326: 862–866PubMedGoogle Scholar
  202. 201.
    Nizankowska E, Soja J, Pinis G et al (1995) Treatment of steroid-dependant bronchial asthma with cyclosporin. Eur Respir J 8: 1091–1099PubMedGoogle Scholar
  203. 202.
    Corrigan CJ, Kay AB (1990) CD4+ T lymphocyte activation in acute severe asthma: relationship to disease severity. Am Rev Respir Dis 140: 970–977Google Scholar

Copyright information

© Springer Basel AG 1999

Authors and Affiliations

  • James L. Lordan
    • 1
  • Ratko Djukanović
    • 1
  1. 1.Level D, Centre Block, Southampton General HospitalUniversity Medicine (810SouthhamptonUK

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