New targets for allergic rhinitis - A disease of civilization

Nature Reviews Drug Discovery

Volumn 2, Issue 11, 2003, Pages 903-914

  Holgate, Stephen T ^a   Broide, David ^b  

^a UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALLERGEN; ANTIHISTAMINIC AGENT; BRADYKININ B2 RECEPTOR AGONIST; CELL ADHESION MOLECULE; CHLORIDE CHANNEL BLOCKING AGENT; CHROMONE DERIVATIVE; CORTICOSTEROID; CROMOGLYCATE DISODIUM; CYTOKINE; DECONGESTIVE AGENT; DNA; GENISTEIN; HISTAMINE H1 RECEPTOR ANTAGONIST; HISTAMINE H4 RECEPTOR ANTAGONIST; IMMUNOGLOBULIN E; LEUKOTRIENE RECEPTOR BLOCKING AGENT; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY MAE11; MONTELUKAST; NEDOCROMIL; OLIGONUCLEOTIDE; PEPTIDE DERIVATIVE; POTASSIUM CHANNEL BLOCKING AGENT; PROSTAGLANDIN RECEPTOR BLOCKING AGENT; SUBSTANCE P; TACHYKININ RECEPTOR ANTAGONIST; TRYPTASE INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; VACCINE; ZAFIRLUKAST;

ALLERGIC ASTHMA; ALLERGIC DISEASE; ALLERGIC RHINITIS; ATOPY; CLINICAL TRIAL; DRUG DESIGN; DRUG EFFICACY; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG TARGETING; DRUG TOLERANCE; HUMAN; IMMUNOTHERAPY; INFLAMMATORY DISEASE; LEUKOCYTE ACTIVATION; LIFESTYLE; MAST CELL; NONHUMAN; NOSE MUCOSA; PREVALENCE; PREVENTION; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; TH2 CELL; WESTERN HEMISPHERE;

EID: 0242690217     PISSN: 14741776     EISSN: None     Source Type: Journal    
DOI: 10.1038/nrd1224     Document Type: Review

References (131)

1. Skoner, D. P. Allergic rhinitis: definition, epidemiology, pathophysiology, detection and diagnosis. J. Allergy Clin. Immunol. 108, S2-S8 (2001).
2. Law, A. W., Reed, S. D., Sundy, J. S. & Schulman, K. A. Direct costs of allergic rhinitis in the United States: estimates from the 1996 Medical Expenditure Panel Survey. J. Allergy Clin. Immunol. 111, 296-300 (2003).
3. Sullivan, S. D. & Weiss, K. B. Health economics of asthma and rhinitis. II. Assessing the value of interventions. J. Allergy Clin. Immunol. 107, 203-210 (2001).
4. Crystal-Peters, J., Neslusan, C., Crown, W. H. & Torres, A. Treating allergic rhinitis in patients with comorbid asthma: the risk of asthma-related hospitalizations and emergency department visits. J. Allergy Clin. Immunol. 109, 57-62 (2002).
5. Cookson, W. Genetics and genomics of asthma and allergic diseases. Immunol. Rev. 190, 195-206 (2002).
6. Umetsu, D. T., McIntire, J. J., Akbari, O., Macaubas, C. & De Kruyff, R. H. Asthma: an epidemic of dysregulated immunity. Nature Immunol. 3, 715-720 (2002).
7. Matricardi, P. M., Rosmini, F., Paneta, V., Ferrigao, L. & Bonini, S. Hayfever and asthma in relation to markers of infection in the United States. J. Allergy Clin. Immunol. 110, 381-387 (2002).
8. Kay, A. B. Allergy and allergic diseases. N. Engl. J. Med. 344, 109-113 (2001).
9. Pullerits, T., Praks, L., Ristioja, V. & Lottval, J. Comparison of a nasal glucocorticoid, antileukotriene and a combination of antileukotriene and antihistamine in the treatment of seasonal allergic rhinitis. J. Allergy Clin. Immunol. 109, 949-955 (2002).
10. Oppenheimer, J. J. & Casale, T. B. Next generation antihsitamines: therapeutic rationale, accomplishments and advances. Expert Opin. Investig. Drugs. 11, 807-817 (2002).
11. 1-receptor antagonists. Allergy 55 (Suppl 64), 17-27 (2000).
12. 2 receptor mediates chemotaxis and calcium mobilization of mast cells. J. Pharmacol. Exp. Ther 305, 1212-1221 (2003 ).
13. 4 concentration in patients with seasonal allergic rhinitis. Allergy 58, 476-480 (2003).
14. Philip, G. et al. Montelukast for treating seasonal allergic rhinitis: a random double-blind, placebo-controlled trial performed in the sprin. Clin. Exp. Allergy 32, 1020-1028 (2002).
15. Topuz, B. & Ogmen, G. G. Monelukast as an adjuvant to mainstay therapies in patients seasonal allergic rhinitis. Clin. Exp. Allergy 33, 823-826 (2003).
16. Nayak, A. S., Philip, G., Lu, S., Malice, M. P. & Reiss, T. F. Efficacy and tolerability of montelukast alone or in combination with loratadine in seasonal allergic rhinitis: a multicentre, randomized, double-blind, placebo-controlled trial performed in the fall. Ann. Allergy Asthma Immunol. 88, 592-600 (2002).
17. Evans, J. F. Cysteinyl leukotriene receptors. Prostaglandins Other Lipid Mediat. 68-69, 587-597 (2002).
18. Arimura, A. et al. Prevention of allergic inflammation by a novel prostaglandin receptor antagonist, S-5751. J. Pharmacol. Exp. Ther. 298, 411-419 (2001).
19. 2-induced eosinophil migration in vitro. J. Pharmacol. Exp. Ther. 305, 347-352 (2003).
20. Vanderslice, P. et al. Human mast cell tryptase: Multiple cDNAs and genes reveal a multigene serine protease family. Proc. Natl Acad. Sci. USA 87, 3811-3815 (1990).
21. Wong, G. W. et al. Biochemical and functional characaterization of human transmembrane tryptase (TMT), tryptase-γ. J. Biol. Chem. 277, 41906-41915 (2003).
22. Newhouse, B. J. Tryptase inhibitors - Review of the recent patent literature. IDrugs 5, 682-688 (2002).
23. Boye, J. A. Mast cells: beyond IgE. J. Allergy Clin. Immunol. 111, 24-32 (2003).
24. Duan, W. et al. Antiinflammatory effects of genistein, a tyrosine kinase inhibitor on a guinea pig model of asthma. Am. J. Respir. Crit. Care Med. 167, 185-192 (2003).
25. Katz, H. R. et al. Mouse mast cell gp 49B1 contains two immunoreceptor tyrosine-based inhibition motifs and suppresses mast cell activation when colligated with the high affinity receptor for IgE. Proc. Natl Acad. Sci. USA 93, 10809-10814 (1996).
26. Daheshia, M. et al. Increased severity of local and systemic anaphylactic reactions in gp49B1-deficient mice. J. Exp. Med. 194, 227-233 (2001).
27. Costa, J. J. et al. Recombinant human stem cell factor (kit ligand) promotes human mast cells and melanocyte hyperplasia and functional activation in vivo. J. Exp. Med. 183, 2681-2686 (1996).
28. Tatton, I., Morley, G. M., Chopra, R. & Khwaja, A. The Src-selective kinase inhibitor PP1 also inhibits Kit and B tyrosine kinases. J. Biol. Chem. 278, 4847-4853 (2003).
29. Duffy, S. M., Lawley, W. J., Conley, E. C. & Brooding, P. Resting and activation-dependent ion channels in human mast cells. J. Immunol. 167, 4261-4270 (2001).
30. Bradding, P., Okayama, Y., Kambe, N. & Saito, H. Ion channel gene expression in human lung, skin and cord blood derived mast cells. J. Leukoc. Biol. 73, 614-620 (2003).
31. Baraniak, S. N. Sensory parasympathetic and sympathetic neural influences in the nasal mucosa. J. Allergy Clin. Immunol. 90, 1045-1050 (1992).
32. Barnes, P. J. Neurogenetic inflammation in the airways. Respir. Physiol. 125, 145-154 (2001).
33. Fajac, I., Braunstein, G., Ickovic, M. R., Lacranicque, J. & Frossard, N. Selective recruitment of eosinophils by substance P after repeated allergen exposure in allergic rhinitis. Allergy 50, 970-975 (1995).
34. 2 kinin receptor antagonist, of antigen-induced nasal blockage. Br. J. Pharmacol. 111, 969-971 (1994).
35. Uddman, R., Cantera, L., Cordell, L. O. & Edvinnsson, L. Expression of NPY Y1 and CGRP1 receptors in human nasal mucosa: implications in allergic rhinitis. Ann. Otol. Rhinol. Laryngol. 108, 969-973 (1999).
36. Korsegren, M. et al. Neural expression and increased lavage fluid levels of secretoneurin in seasonal allergic rhinitis. Am. J. Respir. Crit. Care Med. 167, 1504-1508 (2003).
37. Duzendorfer, S. et al. Secretoneurin, a novel neuropeptide is a potent chemoattractant for human eosinophils. Blood 91, 1527-1532 (1998).
38. Frew, A. J. Immunotherapy of allergy disease. J. Allergy Clin. Immunol. 111, S712-S719 (2003).
39. Nelson, H. S. Advances in upper airway diseases and allergen immunotherapy. J. Allergy Clin. Immunol. 111, S793-S798 (2003).
40. Moller, C. et al. Pollen Immunotherapy reduces the development of asthma in children with seasonal rhinoconjunctivitis (the PAT study) J. Allergy Clin. Immunol. 109, 251-256 (2002).
41. Pajno, G. B., Barberio, G., De Luca, F., Morabito, L. & Parmiani, S. Prevention of new sensitizations in asthmatic children monosensitized to house dust mite by specific immunotherapy. A six-year follow-up study. Clin. Exp. Allergy 31, 1392-1397 (2001).
42. Malling, H. J. Is sublingual immunotherapy clinically effective? Curr. Opin. Allergy Clin. Immunol. 2, 523-531 (2002).
43. Durham, S. R. et al. Long-term clinical efficacy of grass-pollen immunotherapy. N. Engl. J. Med. 341, 468-475 (1999).
44. Di Rienzo, V. et al. Long-lasting effect of sub-lingual immunotherapy in children with asthma due to house dust mite: a 10 year prospective study. Clip. Exp. Allergy 33, 206-210. (2003).
45. Canonica, G. W. & Passalacqua, G. Non-injection routes for immunotherapy. J. Allergy Clin. Immunol. 111, 437-448 (2003).
46. H2 cyotkine ratios. Immunology 105, 56-62 (2002).
47. Nasser, S. M., Ying, S., Meng, Q., Kay, A. B. & Ewan, P. W. Interleukin-10 levels increase in cutaneous biopsies of patients undergoing wasp venom immunotherapy. Eur. J. Immunol. 31, 3704-3713 (2001).
48. McHugh, R. S. & Shevach, E. M. The role of suppressor T cells in regulation of immune responses. J. Allergy Clin. Immunol. 110, 693-702 (2002).
49. TePas, E. C. & Umetsu, D. T. Immunotherapy of asthma and allergic disease. Curr. Opin. Pediatr. 12, 574-578 (2000).
50. Hamid, Q. A., Schotman, E., Jacobsen, M. R., Walker, S. M. & Durham, S. R. Increases in IL-12 messenger RNA+ cells accompany inhibition of allergen-induced late skin responses after successful grass pollen immunotherapy. J. Allergy Clin. Immunol. 99, 254-269 (1997).
51. Yazdanbahsh, M., Kremsner, P. G. & van Ree, R. Allergy parasites and the hygiene hypothesis. Science 296, 490-494 (2002).
52. Fontenot, J. D., Gavin, M. A. & Rudensky A. Y. Fox P3 programs the development and function of CD4+CD25+ regulatory T cells. Nature Immunol. 4, 330-336 (2003).
53. Shimizu, J. et al. Stimulation of CD25+ CD4+ regulatory T cells through GITR breaks immunological self-tolerance. Nature Immunol. 3, 135-142 (2002).
54. Bystry R. S., Aluvihare, U., Welch, K. A., Kallikoardis, M. & Betz, A. G. B cells and professional APCs recruit regulatory T cells via CCL4. Nature Immunol. 2, 1126-1132 (2001).
55. Ebner, C. Immunological mechanisms operative in allergen-specific immunotherapy. Int. Arch. Allergy Immunol. 119, 1-5(1999).
56. Briner, T. J., Kuo, M. C., Keating, K. M., Rogers, B. L. & Greenstein, J. L. Peripheral T-cell tolerance induced in naive and primed mice by subcutaneous injection of peptides form the major cat allergen Fel d 1. Proc. Natl Acad. Sci. USA 90, 7608-7612 (1993).
57. Norman, P. S. et al. Treatment of cat allergy with T cell reactive peptides. Am. J. Resp. Crit. Care Med. 154, 1623-1628 (1996).
58. Oldfield, W. L., Larché, M. & Kay, A. B. Effect of T cell peptides derived from fel D 1 on allergic reactions and cytokine production in patients sensitive to cats: a randomised controlled trial. Lancet 360, 47-53 (2002).
59. Haselden, B. M., Kay, A. B. & Larché, M. IgE-dependent MHC-restricted T cell peptide epitope-induced late asthmatic reactions. J. Exp. Med. 189, 1885-1894 (1999).
60. H2-type cells or with elevated concentrations of histamine or eicosanoids in bronchoalveolar fluid. J. Allergy Clin. Immunol. 108, 394-401 (2001).
61. Broide, D. H. & Raz, E. in Lung Biology in Health and Disease Vol 177 (ads Eissa, N. T. & Huston, D. P.) 839-865, (Marcel Dekker, New York, in the press).
62. Horner, A. A., Van Uden, J. H., Zubeldia, J. M., Broide, D. & Raz, E. DNA-based Immunotherapeutics for the treatment of allergic disease. Immunol. Rev. 179, 102-118 (2001).
63. Hemmi, H. et al. A Toll-like receptor recognizes bacterial DNA. Nature 408, 740-745 (2000).
64. Roman, M. et al. Immunostimulatory DNA sequences function as T helper-1-promoting adjuvants. Nature Med. 3, 849-854 (1997).
65. Horner, A. A. et al. Immmunostimulatory DNA inhibits IL-4 dependent IgE synthesis by human B cells. J. Allergy Clin. Immunol. 108, 417-423 (2001).
66. Broide, D. et al. Immunostimulatory DNA sequences inhibit IL-5, eosinophilic inflammation and airway hyperresponsiveness in mice. J. Immunol. 161, 7054-7062 (1998).
67. Kline, J. N. et al. Modulation of airway inflammation by CpG oligodeoxynucleotides in a murine model of asthma. J. Immunol. 160, 2555-2559 (1998).
68. Ikeda, R. K. et al. Resolution of airway inflammation following ovalbumin inhalation: comparison of ISS DNA and corticosteroids. Am. J. Resp. Cell Mol. Biol. 28, 655-683 (2003).
69. Hussain, I. et al. Modulation of murine allergic rhinosinusitis by CpG oligodeoxynucleotides. Layrngoscope 112, 1819-1826 (2002).
70. Creticos, P. et al. Immunotherapy with immunostimulatory oligonucleotides linked to purified ragweed Amb a 1 allergen: Effects on antibody production, nasal allergen provocation, and ragweed seasonal rhinitis. J. Allergy Clin. Immunol. 109, 743-744 (2002).
71. Henderson, W. R. Jr, Chi, E. Y. & Maliszewski, C. R. IL-4 receptor inhibits airway inflammation following allergen challenge in a mouse model of asthma. J. Immunol. 164, 1086-1095 (2000).
72. Cieslewicz, G. et al. The late, but not early, asthmatic response is dependent on IL-5 and correlates with eosinophil infiltration. J. Clin. Invest. 104, 301-308 (1999).
73. H2 cytokine expression in PBMCs from human patients with ragweed allergy. J. Allergy Clin. Immunol. 108, 191-197 (2001).
74. Tighe, H. et al. Conjugation of immunostimulatory DNA to the short ragweed allergen Amb a 1 enhances it immunogenicity and reduces its allergenicity. J. Allergy Clin. Immunol. 106, 124-134 (2000).
75. Chang, T. W. The pharmacological basis of anti-IgE therapy. Nature Biotechnol. 18, 157-163 (2000).
76. Presta, S. R. et al. Humanization of an antibody directed against IgE. J. Immunol. 151, 2623-2632 (1993).
77. Lazaar, A. L. Technology evaluation omalizumab. Genetech/Novartis/Tanox. Curr. Opin. Mol. Ther. 5, 81-89 (2003).
78. Casale, T. B. et al. Effect of omalizumab on symptoms of seasonal allergic rhinitis: a randomized controlled trial. JAMA 286, 2956-2967 (2001).
79. Adelroth, E. et al. Recombinant humanized on A6-E25, an anti-IgE mAb, in birch-pollen-induced seasonal allergic rhinitis. J. Allergy Clin. Immunol. 106, 253-259 (2000).
80. Kuehr, J. et al. Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis. J. Allergy Clin. Immunol. 109, 274-280 (2002).
81. Plewako, H. et al. The effect of omalizumab on nasal allergic inflammation. J. Allergy Clin. Immunol. 110, 68-71 (2002).
82. cR1 expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J. Immunol. 158, 1438-1445 (1997).
83. cR1 on antigen presenting cells. J. Allergy Clin. Immunol. 111, 38-44 (2003).
84. Vernesson, M., Ledin, A., Johansson, J. & Heilman, L. Generation of therapeutic antibody response against IgE through vaccination. FASEB J. 16, 875-877 (2002).
85. Nadler, M. J. & Kinet, J. P. Uncovering new complexities in mast cell signalling. Nature Immunol. 3, 707-708 (2002).
86. Christodoulopulos, P., Cameron, L., Durham, S. & Hamid, Q. Molecular pathology of allergic disease. II: Upper airway disease. J. Allergy Clin. Immunol. 105, 211-223 (2000).
87. Wills-Karp, M. Immunology basis of antigen-induced airway hyperresponsiveness. Annu. Rev. Immunol. 17, 255-281 (1999).
88. Foster, P. S. et al. Interleukin-5 and eosinophils as therapeutic targets for asthma. Trends Mol. Med. 8, 162-167 (2002).
89. Borish, L. C et al. Efficacy of soluble IL-4 receptor for the treatment if adults with asthma. J. Allergy Clin. Immunol. 107, 963-970 (2001).
90. Borrish, L. C. et al. Interleukin-4 receptor in moderate atopic asthma. A phase 1/randomized, placebo-controlled trial. Am. J. Respir. Crit. Care Med. 160, 1816-1823 (1999).
91. Atamas, S. P., Choi, J., Yurovsky, V. V. & White, B. An alternative splice variant of human IL-4, IL-4 inhibits IL-4 stimulated T cell proliferation. J. Immunol. 156, 435-441 (1996).
92. Kruse, N., Tony, H. P. & Sebald, W. Conversion of human IL-4 into a high affinity antagonist by a single aminoacid replacement. EMBO J. 11, 3237-3244 (1992).
93. Wills-Karp, M. et al. Interleukin 13: central mediator of allergic asthma. Science 282, 2258-2261 (1998).
94. Skowron, M., Peret, E., Marano, F., Caput, D. & Tournier, F. Intelruekin-13 alters mucociliary differentiation of human nasal epithelial cells. Chest 123, 373S-374S (2003).
95. Wynn, T. A. IL-13 effector functions. Annu. Rev. Immunol. 21, 425-456 (2003).
96. Kleinjan, A. et al. Increase in IL-8, IL-10, IL-13 and RANTES mRNA levels (in situ hybridization) in the nasal mucosa after nasal allergen provocation. J. Allergy Clin. Immunol. 103, 441-450 (1999).
97. Andrews, A. L., Holloway, J. W., Puddicombe, S. L., Holgate, S. T. & Davies, D. E. Kinetic analysis of interleukin-13 receptor complex. J. Biol. Chem. 227, 46073-46078 (2003).
98. Wood, N. et al. Enhanced interleukin (IL)-13 responses in mice lacking IL-13 receptor α2. J. Exp. Med. 197, 703-709 (2003).
99. Wills-Karp, M. & Chiaramonte, M. Interleukin-13 in asthma. Curr. Opin. Pulm. Med. 9, 21-27 (2003).
100. Wills-Karp, M. Murine models of asthma in understanding immune dysregulation in human asthma. Immopharmacology 48, 263-268 (2000).
101. Oshima, Y. & Puri, R. A novel antagonist that blocks the biological activity of human IL-13 in immune and non-immune cells. FASEB J. 15, 1469-1471 (2001).
102. Leckie, M. J. et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyperresponsiveness and the late asthmatic response. Lancet 356, 2144-2148 (2000).
103. Kips, J. C. et al. Effect of SECH 55700, a humanized anti-human interleukin-5 antibody in severe persistent asthma. Am. J. Respir. Crit. Care Med. 167, 1655-1659 (2003).
104. Flood-Page, P. T., Menzies-Gow, A. N., Kay, A. B. & Robinson, D. S. Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am. J. Respir. Crit. Care Med. 167, 199-204 (2003).
105. Saito, H. et al. Pathogenesis of murine experimental allergic rhinitis: a study of local and systemic consequences of IL-5 deficiency. J. Immunol. 168, 3017-3023 (2003).
106. Zhou, C. Y., Crocker, I. C., Koenig, G., Romero, F. A. & Townley, R. G. Anti-Interlukin-4 inhibits IgE production in a murine model of atopic asthma. J. Asthma 34, 195-201 (1997).
107. Tanaka, H., Nagai, H. & Macda, Y. Effect of anti IL-4 and anti-IL-5 antibodies on allergic airway hyperresponsiveness in mice. Life Sci. 62, PL169-PL174 (1998).
108. Terada, N. et al. The kinetics of allergen-induced eotaxin level in nasal lavage fluid: its key role in eosinophil recruitment in nasal mucosa. Am. J. Respir. Crit. Care Med. 164, 575-579 (2001).
109. Gorski, P. et al. Eotaxin but not MCP-3 induces eosinophil influx into nasal fluid in allergic patients. Allergy 57, 519-528 (2002).
110. Cooper, J. A. Jr., Ridgeway, A. L., Pearson, J. & Culbreth, R. R. Attenuation of interleukin 8-induced nasal inflammation by an inhibitor peptide. Am. J. Respir. Crit. Care Med. 163, 1198-1205 (2001).
111. Mattes, J. et al. Intrinsic defect in T cell production of interleukin (IL)-13 in the absence of both IL-5 and eotaxin precludes the development of eosinophilia and airways hyperreacitivity in experimental asthma. J. Exp. Med. 195, 1433-1444 (2002).
112. Von Hertzen, L. & Haahtela, T. Could the risk of asthma and atopy be reduced by a vaccine that induces a strong T-helper Type 1 response? Am. J. Respir. Cell Mol. Biol. 22, 139-142 (2000).
113. Barnes, P. J. Cytokine-directed therapies in asthma. Allergol. Int. 52, 53-63 (2003).
114. Bryan, S. A. et al. Effects of recombinant human interleukin-12 on eosinophils, airway hyperresponsiveness and the late asthmatic response. Lancet 356, 2149-2153 (2000).
115. Castro, M., Chaplin, D. D., Walter, M. J. & Holtzman, M. J. Could asthma be worsened by stimulation of the T-helper Type 1 immune response? Am. J. Respir. Cell Mol. Biol. 22, 143-146 (2000).
116. Zuang-Amorim, C. et al. Long-term protective and antigenspecific effect of heat killed Mycobacterium vaccae in a murine model of allergic pulmonary inflammation. J. Immunol. 169, 1492-1499 (2002).
117. Camporota, L. et al. The effect of Mycobacterium vaccae on allergen-induced airway response in atopic asthma. Eur. Respir. J. 21, 287-293 (2003).
118. Zuang-Amorin, C. et al. Suppression of airway eosinophila by killed mycobacterium vaccae-induced allergen-specific regulatory T cells. Nature Med. 8, 625-629 (2002).
119. Kalliomäki, M. et al. Probiotics in the primary prevention of atopic disease: a randomised placebo controlled trial. Lancet 357, 1076-1079 (2001).
120. Helin, T, Haahtela, S. & Haahtela, T. No effect of oral treatment with an intestinal bacterial strain, Lactobacillus rhamnosus (ATCC 53103) on birch pollen allergy: a placebo-controlled double-blind study. Allergy 57, 243-246 (2002).
121. Braunstahl, G. H. et al. Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways. J. Allergy Clin. Immunol. 107, 469-476 (2001).
122. Symon, F. A., Walsh, G. M., Watson, S. R. & Wardlaw, A. J. Eosinophil adhesion to nasal polyp endothelium is P-selectin dependent. J. Exp. Med. 180, 371-376 (1994).
123. Broide, D. H., Sullivan, S., Gifford, T. & Sriraarao, P. Inhibition of pulmonary eosinophilia in P-selectin- and ICAM-1-deficient mice. Am. J. Respir. Cell Mol. Biol. 18, 218-225 (1998).
124. Sriramarao, P. et al. E-selectin preferentially supports neutrophils but not eosinophil rolling under conditions of flow in vitro and in vivo. J. Immunol. 157, 4672-4680 (1996).
125. Jackson, D. Y. α integrin antagonists. Curr. Pharm. Des. 8, 1229-1253 (2002).
126. Anwar, A. R., Moqbel, R., Walsh, G. M., Kay, A. B. & Wardlaw, A. J. Adhesion to fibronectin prolongs eosinophil survival. J. Exp. Med. 177, 839-843 (1993).
127. Henderson, W. R. Jr. et al. Blockade of CD49d (α4 integrin) on intrapulmonary but not circulating leukocytes inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma. J. Clin. Invest. 100, 3083-3092 (1997).
128. Abraham, W. M. et al. A small-molecule, tight-binding inhibitor of the integrin α4β1 blocks antigen-induced airway responses and inflammation in experimental asthma in sheep. Am. J. Respir. Crit. Care Med. 162, 602-661 (2000).
129. Giembycz, C. A. Phosphodiesterase 4 inhibitors and the treatment of asthma. Drugs 59, 193-212 (2002).
130. Schmidt, B. M. et al. The phosphodiesterase 4 inhibitor rofulimast is effective in the treatment of allergic rhinitis. J. Allergy Clin. Immunol. 108, 503-506 (2001).
131. Sorbera, L. A., Leeson, P. A. & Castaner, J. Rofumilast, BY-217. Drugs of the Future 25, 1261-1264 (2000).