Cytokine and anti-cytokine therapy in asthma: Ready for the clinic?

Clinical and Experimental Immunology

Volumn 158, Issue 1, 2009, Pages 10-19

  Desai, D ^a   Brightling, C ^a  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

Airway hyperresponsiveness; Anti IL 5; Anti TNF ; Asthma; Cytokines; Exacerbations

Indexed keywords

ALPHA INTERFERON; ALTRAKINCEPT; AMG 317; ANTIASTHMATIC AGENT; CORTICOSTEROID; CYTOKINE; CYTOKINE ANTIBODY; ETANERCEPT; GOLIMUMAB; IMA 638; INFLIXIMAB; INTERFERON; INTERFERON ALPHACON 1; INTERLEUKIN 13 ANTIBODY; INTERLEUKIN 4; INTERLEUKIN 5 ANTIBODY; MEDI 528; MEDI 563; MEPOLIZUMAB; MONOCLONAL ANTIBODY; PASCOLIZUMAB; PITRAKINRA; PLACEBO; RECOMBINANT GAMMA INTERFERON; RECOMBINANT INTERLEUKIN 10; RECOMBINANT INTERLEUKIN 12; SCH 55 700; TUMOR NECROSIS FACTOR ALPHA ANTIBODY; UNCLASSIFIED DRUG;

ASTHMA; CLINICAL ASSESSMENT; CLINICAL TRIAL; DISEASE EXACERBATION; DRUG DOSE ESCALATION; DRUG EFFECT; DRUG EFFICACY; DRUG MEGADOSE; DRUG WITHDRAWAL; ENTERITIS; FLU LIKE SYNDROME; FORCED EXPIRATORY VOLUME; HEART ARRHYTHMIA; HUMAN; LIVER FUNCTION TEST; MORBIDITY; MORTALITY; NONHUMAN; PNEUMONIA; PREVALENCE; PRIORITY JOURNAL; PROTEIN TARGETING; PSORIASIS; RESPIRATORY TRACT INFLAMMATION; REVIEW; RHEUMATOID ARTHRITIS; SEPSIS; SIDE EFFECT; TH2 CELL; TREATMENT OUTCOME;

ANTI-ASTHMATIC AGENTS; ANTIBODIES, MONOCLONAL; ASTHMA; CYTOKINES; HUMANS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECOMBINANT PROTEINS;

EID: 69949132843     PISSN: 00099104     EISSN: 13652249     Source Type: Journal    
DOI: 10.1111/j.1365-2249.2009.03998.x     Document Type: Review

References (80)

1. Braman SS. The Global Burden of asthma. Chest. 2006 130 (1 Suppl. 4S 12S.
2. British Thoracic Society/Scottish Intercollegiate Guidelines Network. British Guideline on Management of Asthma. 05/08. Available at: http://www.brit-thoracic.org.uk (accessed 30 April 2009).
3. Global Initiative for Asthma Guidelines 11/06. Available at: http://www.ginasthma.com (accessed 30 April 2009).
4. Chanez P, Wenzel SE, Anderson GP et al. Severe asthma: what are the important questions? J Allergy Clin Immunol 2008 119 : 1337 1348.
5. Proceedings of the ATS Workshop on Refractory Asthma. Current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med 2000 162 : 2341 2351.
6. Haldar P, Pavord ID, Shaw DE et al. Cluster analysis and clinical asthma phenotypes. Am J Respir Crit Care Med 2008 178 : 218 224.
7. Green RH, Brightling CE, McKenna S et al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet 2002 360 : 1715 1721.
8. Jayaram L, Pizzichini MM, Cook RJ et al. Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations. Eur Respir J 2006 27 : 483 494.
9. Brightling CE, Berry M, Amrani Y. Anti-TNF-α in asthma. J Allergy Clin Immunol 2008 121 : 5 10.
10. Tarantini F, Baiardini I, Passalacqua G, Braido F, Canonica GW. Asthma treatment: 'magic bullets which seek their own targets'. Allergy 2007 62 : 605 610.
11. Walker S, Monteil M, Phelan K, Lasserson TJ, Walters EH. Anti-IgE for chronic asthma in adults and children. Cochrane Database of Systematic Reviews, 2006, Issue 2. Art. no.: CD003559. DOI: 10.1002/14651858.CD003559.pub3.
12. Wardlaw AJ, Brightling C, Green R, Woltmann G, Pavord I. Eosinophils in asthma and other allergic diseases. Br Med Bull 2000 56 : 985 1003.
13. Humbles AA, Lloyd CM, McMillan SJ et al. A critical role for eosinophils in allergic airways remodelling. Science 2004 305 : 1776 1779.
14. Wardlaw AJ, Brightling CE, Green R, Woltmann G, Bradding P, Pavord ID. New insights into the relationship between airway inflammation and asthma. Clin Sci (Lond) 2002 103 : 201 211. (Pubitemid 34886313)
15. Brightling CE, Bradding P, Pavord ID, Wardlaw AJ. New insights into the role of the mast cell in asthma. Clin Exp Allergy 2003 33 : 550 556. (Pubitemid 36629677)
16. Haldar P, Pavord ID. Noneosinophilic asthma: a distinct clinical and pathologic phenotype. J Allergy Clin Immunol 2007 119 : 1043 1052.
17. Holgate ST. Novel targets of therapy in asthma. Curr Opin Pulm Med 2009 15 : 63 71.
18. Pepe C, Foley S, Shannon J et al. Differences in airway remodelling between subjects with severe and moderate asthma. J Allergy Clin Immunol 2005 166 : 544 549.
19. Hammad H, Lambrecht BN. Recent progress in the biology of airway dendritic cells and implications for understanding the regulation of asthmatic inflammation. J Allergy Clin Immunol 2006 118 : 331 336.
20. Medoff BD, Thomas SY, Luster AD. T cell trafficking in allergic asthma: the ins and outs. Annu Rev Immunol 2008 26 : 205 232.
21. Larché M, Robinson DS, Kay AB. The role of T lymphocytes in the pathogenesis of asthma. J Allergy Clin Immunol 2003 111 : 450 463.
22. Robinson DS, Hamid Q, Ying S et al. Predominant TH-2 like bronchoalveolar T-lymphocyte populations in atopic asthma. N Engl J Med 1992 326 : 298 304.
23. Brightling CE, Symon FA, Birring SS, Bradding P, Pavord ID, Wardlaw AJ. Th2 cytokine expression in bronchoalveolar lavage fluid T-lymphocytes and bronchial submucosa is a feature of asthma and eosinophilic bronchitis. J Allergy Clin Immunol 2002 110 : 899 905.
24. Brightling CE, Bradding P, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID. Interleukin-4 and -13 expression is co-localized to mast cells within the airway smooth muscle in asthma. Clin Exp Allergy 2003 33 : 1711 1716.
25. Saha SK, Berry MA, Parker D et al. Increased sputum and bronchial biopsy IL-13 expression in severe asthma. J Allergy Clin Immunol 2008 121 : 685 691.
26. Humbert M, Corrigan CJ, Durham SR, Kimmit P, Till SJ, Kay AB. Relationship between bronchial mucosal IL-4 and IL-5 mRNA expression and disease severity in atopic asthma. Am J Respir Crit Care Med 1997 156 : 704 708.
27. Humbert M, Durham SR, Kimmitt P et al. Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma. J Allergy Clin Immunol 1997 99 : 657 665.
28. Broide DH, Firestein GS. Endobronchial allergen challenge in asthma. Demonstration of cellular source of granulocyte macrophage colony-stimulating factor by in situ hybridization. J Clin Invest 1991 88 : 1048 1053.
29. Saha SK, Doe C, Mistry V et al. Granulocyte macrophage colony stimulating factor expression in induced sputum and bronchial mucosa in asthma and COPD. Thorax. 2009 Thorax Online First, published 12 February 2009 as 10.1136/thx.2008.108290
30. Grunig G, Warnock M, Wakil AE et al. Requirement for IL-13 independently of IL-4 in experimental asthma. Science 1998 282 : 2261 2263.
31. Zhu Z, Homer RJ, Wang Z et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest 1999 103 : 779 788.
32. Su YC, Rolph MS, Hansbro NG, Mackay CR, Sewell WA. Granulocyte-macrophage colony stimulating factor is required for bronchial eosinophilia in a murine model of allergic airway inflammation. J Immunol 2008 180 : 2600 2607.
33. Ying S, Robinson DS, Varney V et al. TNF alpha mRNA expression in allergic inflammation. Clin Exp Allergy 1991 21 : 745 750.
34. Bradding P, Roberts JA, Britten KM et al. Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. Am J Respir Cell Mol Biol 1994 10 : 471 480.
35. Howarth PH, Babu KS, Arshad HS et al. Tumour necrosis factor (TNFα) as a novel therapeutic target in symptomatic corticosteroid dependent asthma. Thorax 2005 60 : 1012 1018.
36. Berry MA, Hargadon B, Shelley M et al. Evidence of a role of tumour necrosis factor alpha in refractory asthma. N Engl J Med 2006 354 : 697 708.
37. Brightling CE, Bradding P, Symon FA, Holgate ST, Wardlaw AJ, Pavord ID. Mast cell infiltration of airway smooth muscle in asthma. N Engl J Med 2002 346 : 1699 1705.
38. Carroll NG, Mutavdzic S, James AL. Distribution and degranulation of airway mast cells in normal and asthmatic subjects. Eur Respir J 2002 19 : 879 885.
39. Berger P, Girodet PO, Begueret H et al. Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis. FASEB J 2003 17 : 2139 2141.
40. Slats AM, Janssen K, van Schadewijk A et al. Bronchial inflammation and airway responses to deep inspiration in asthma and COPD. Am J Respir Crit Care Med 2007 176 : 121 128.
41. Siddiqui S, Mistry V, Doe C et al. Airway hyperresponsiveness is dissociated from airway wall structural remodeling. J Allergy Clin Immunol 2008 122 : 335 341.
42. Amin K, Janson C, Boman G, Venge P. The extracellular deposition of mast cell products is increased in hypertrophic airways smooth muscles in allergic asthma but not in nonallergic asthma. Allergy 2005 60 : 1241 1247.
43. Siddiqui S, Brightling CE. Microlocalisation of inflammatory cells and structural cells: functional consequences in airways disease. Eur Respir J 2007 30 : 1043 1056.
44. Tliba O, Deshpande D, Chen H et al. IL-13 enhances agonist-evoked calcium signals and contractile responses in airway smooth muscle. Br J Pharmacol 2003 140 : 1159 1162.
45. Laporte JC, Moore PE, Baraldo S et al. Direct effects of interleukin-13 on signalling pathways for physiological responses in cultured human airway smooth muscle cells. Am J Respir Crit Care Med 2001 164 : 141 148.
46. Grunstein MM, Hakonarson H, Leiter J et al. IL-13 dependent autocrine signalling mediates altered responsiveness of IgE-sensitized airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 2002 282 : 520 528.
47. Woodman L, Siddiqui S, Cruse G et al. Mast cells promote airway smooth muscle cell differentiation via autocrine upregulation of TGF-β1. J Immunol 2008 181 : 5001 5007.
48. Wenzel S. Severe asthma in adults. Am J Resp Crit Care Med 2005 172 : 149 160. (Pubitemid 40981187)
49. Kamath AV, Pavord AV, Ruparelia PR, Chilvers ER. Is the neutrophil the key effector cell in severe asthma? Thorax 2005 60 : 529 530.
50. Idris SF, Chilvers ER, Haworth C, McKeon D, Condliffe AM. Azithromycin therapy for neutrophilic airways disease: myth or magic? Thorax 2009 64 : 186 189.
51. Benayoun L, Druilhe A, Dombret M-C, Aubier M, Pretolani M. Airway structural alterations selectively associated with severe asthma. Am J Resp Crit Care Med 2003 167 : 1360 1368.
52. Leckie MJ, ten Brinke A, Khan J et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet 2000 356 : 2144 2148.
53. Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS. Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med 2003 167 : 199 204.
54. Kips J, O'Connor BJ, Langley SJ et al. Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study [abstract Am J Respir Crit Care Med 2003 167 : 1655 1659.
55. Flood-Page P, Swenson C, Faiferman I et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med 2007 176 : 1062 1071.
56. Haldar P, Brightling CE, Hargadon B et al. Meoplizumab and exacerbations of eosinophilic refractory asthma. N Engl J Med 2009 360 : 973 984.
57. Nair P, Pizzichini MM, Kjarsgaard M et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009 360 : 985 993.
58. Flood-Page P, Menzies-Gow A, Phipps S et al. Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J Clin Invest 2003 112 : 1029 1036.
59. Borish LC, Nelson HS, Lanz MJ et al. Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebo-controlled trial. Am J Respir Crit Care Med 1999 160 : 1816 1823.
60. Borish LC, Nelson HS, Corren J et al. Efficacy of soluble IL-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol 2001 107 : 963 970.
61. Hart TK, Blackburn MN, Brigham-Burke M et al. Preclinical efficacy and safety of pascolizumab (SB240683): a humanised anti-interleukin-4 antibody with therapeutic potential in asthma. Clin Exp Immunol 2002 130 : 93 100.
62. Wenzel S, Wilbraham D, Fuller R, Getz EB, Longphre M. Effect of an interleukin-4 variant on late phase asthmatic response to allergen challenge in asthmatic patients: results of two phase 2a studies. Lancet 2007 370 : 1422 1431.
63. Getz EB, Wilbraham D, Lalor C, Longphre M, Fuller R. Pharmacokinetics and local tolerance of an IL-4/IL-13 antagonist inhalation powder in humans. ERS Conference 2008 : 545S (abstract). Available at: http://www.ersnet.org
64. Gauvreau GM, Boulet LP, Fitzgerald JM et al. The effects of IMA-638 on allergen induced airway responses in subjects with mild atopic asthma. ERS Conference 2008 : 827S (abstract). Available at: http://www.ersnet.org
65. Bhowmick B, Singh D, Molfino N et al. A double-blind, placebo-controlled, study to assess the pharmacokinetics, safety and tolerability of multiple ascending intravenous doses of CAT 354, a recombinant human anti-IL13 antibody, in subjects with moderate asthma. ERS Conference 2008 : 515S (abstract). Available at: http://www.ersnet.org
66. Banfield C, Vincent M, Kakkar T et al. Multiple-dose study of AMG317 in adults with asthma: pharmacokinetics and safety. Am J Respir Crit Care Med 2008 177 : A568.
67. O'Byrne P, Boulet L-P, Gauvreau G, Leon F, Sari S, White B. A single dose of MEDI-528, a monoclonal antibody against interleukin-9, is well tolerated in mild and moderate asthmatics in the phase II trial MI-CP-138. Chest 2007 132 : 478.
68. Boguniewicz M, Martin RJ, Martin D et al. The effects of nebulised recombinant interferon-γ in asthmatic airways. J Allergy Clin Immunol 1995 95 : 133 135.
69. Simon HU, Seelbach H, Ehmann R, Schmitz M. Clinical and immunological effects of low-dose IFNα treatment in patients with corticosteroid- resistant asthma. Allergy 2003 58 : 1250 1255.
70. Kroegel C, Bergmann N, Foerster M et al. Interferon-alphacon-1 treatment of three patients with severe glucocorticoid-dependent asthma. Effect on disease control and systemic glucocorticoid dose. Respiration 2006 73 : 566 570.
71. Bryan SA, O'Connor BJ, Matti S et al. Effects of recombinant human interleukin-12 on eosinophils, airway hyperresponsiveness, and the late asthmatic response. Lancet 2000 356 : 2149 2153.
72. Chernoff AE, Granowitz EV, Shapiro L et al. A randomised, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses. J Immunol 1995 154 : 5492 5499.
73. Erin EM, Leaker BR, Nicholson GC et al. The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma. Am J Respir Crit Care Med 2006 174 : 753 762.
74. Morjaria JB, Chauhan AJ, Babu KS, Polosa R, Davies DE, Holgate ST. The role of a soluble TNFα receptor fusion protein (Etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial. Thorax 2008 63 : 584 591.
75. Wenzel SE, Barnes PJ, Bleecker ER et al. A randomized, double-blind, placebo-controlled study of tumor necrosis factor-α blockade in severe persistent asthma. Am J Respir Crit Care Med 2009 179 : 549 558.
76. Rennard SI, Fogarty C, Kelsen S et al. The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2007 175 : 926 934.
77. Louten J, Boniface K, de Waal Malefyt R. Development and function of Th17 cells in health and disease. J Allergy Clin Immunol 2009 123 : 1004 1011.
78. Al-Ramli W, Préfontaine D, Chouiali F et al. Th-17 associated cytokines (IL-17A and IL-17F) in severe asthma. J Allergy Clin Immunol 2009 123 : 1185 1187.
79. Ballantyne SJ, Barlow JL, Jolin HE et al. Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. J Allergy Clin Immunol 2007 120 : 1234 1231.
80. Hayakawa H, Hayakawa M, Kume A, Tominaga S. Soluble ST blocks interleukin-33 signalling in allergic airway inflammation. J Biol Chem 2007 282 : 26369 26380.