The Journal of Allergy and Clinical Immunology
Volume 121, Issue 1 , Pages 5-10 , January 2008

Targeting TNF-α: A novel therapeutic approach for asthma

  • Christopher Brightling, PhD, MRCP

      Affiliations

    • Institute of Lung Health, University of Leicester, Leicester, United Kingdom
    • Corresponding Author InformationReprint requests: Christopher Brightling, PhD, MRCP, Institute of Lung Health, University of Leicester, Leicester, LE3 9QP, United Kingdom.
    • ,
  • Mike Berry, MD, MRCP

      Affiliations

    • University of Birmingham, Edgbaston, Birmingham, United Kingdom
    • ,
  • Yassine Amrani, PhD

      Affiliations

    • Institute of Lung Health, University of Leicester, Leicester, United Kingdom

Received 11 September 2007 ,Revised 15 October 2007 ,Accepted 16 October 2007.

References 

  1. Bousquet J, Bousquet PJ, Godard P, Daures JP. The public health implications of asthma. Bull World health Organ. 2005;83:548–554
  2. Braman SS. The global burden of asthma. Chest. 2006;130(suppl):4S–12S
  3. Global Initiative for Asthma guidelines 11/06. Available at: http://www.ginasthma.com. Accessed August 2007.
  4. American Thoracic Society . Proceedings of the ATS workshop on refractory asthma: current understanding, recommendations, and unanswered questions. Am J Respir Crit Care Med. 2000;162:2341–2351
  5. Moore WC, Peters SP. Severe asthma: an overview. J Allergy Clin Immunol. 2006;117:487–494
  6. Chanez P, Wenzel SE, Anderson GP, Anto JM, Bel EH, Boulet LP, et al. Severe asthma in adults: what are the important questions?. J Allergy Clin Immunol. 2007;119:1337–1348
  7. Howarth PH, Babu KS, Arshad HS, Lau L, Buckley M, McConnell W, et al. Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma. Thorax. 2005;60:1012–1018
  8. Berry MA, Hargadon B, Shelley M, Parker D, Shaw SE, Green RH, et al. Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med. 2006;354:697–708
  9. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295:2275–2285
  10. Green RH, Brightling CE, Bradding P. The reclassification of asthma based on subphenotypes. Curr Opin Allergy Clin Immunol. 2007;7:43–50
  11. Wenzel SE. Asthma: defining of the persistent adult phenotypes. Lancet. 2006;368:804–813
  12. Medzhitov R, Janeway C. Innate immunity. N Engl J Med. 2000;343:338–344
  13. Cazzola M, Polosa R. Anti-TNF-alpha and Th1 cytokine-directed therapies for the treatment of asthma. Curr Opin Allergy Clin Immunol. 2006;6:43–50
  14. Kriegler M, Perez C, DeFay K, Albert I, Lu SD. A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell. 1988;53:45–53
  15. Zheng Y, Saftig P, Hartmann D, Blobel C. Evaluation of the contribution of different ADAMs to tumor necrosis factor alpha (TNFalpha) shedding and of the function of the TNFalpha ectodomain in ensuring selective stimulated shedding by the TNFalpha convertase (TACE/ADAM17). J Biol Chem. 2004;279:42898–42906
  16. Smith RA, Baglioni C. The active form of tumor necrosis factor is a trimer. J Biol Chem. 1987;262:6951–6954
  17. Brockhaus M, Schoenfeld HJ, Schlaeger EJ, Hunziker W, Lesslauer W, Loetscher H. Identification of two types of tumor necrosis factor receptors on human cell lines by monoclonal antibodies. Proc Natl Acad Sci U S A. 1990;87:3127–3131
  18. Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med. 2001;344:907–916
  19. Olsen NJ, Stein CN. New drugs for rheumatoid arthritis. N Engl J Med. 2004;350:2167–2179
  20. Ying S, Robinson DS, Varney V, Meng Q, Tsicopoulos A, Moqbel R, et al. TNF alpha mRNA expression in allergic inflammation. Clin Exp Allergy. 1991;21:745–750
  21. Bradding P, Roberts JA, Britten KM, Montefort S, Djukanovic R, Mueller R, 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
  22. Thomas PS, Yates DH, Barnes PJ. Tumor necrosis factor-alpha increases airway responsiveness and sputum neutrophilia in normal human subjects. Am J Respir Crit Care Med. 1995;152:76–80
  23. Thomas PS, Heywood G. Effects of inhaled tumour necrosis factor alpha in subjects with mild asthma. Thorax. 2002;57:774–778
  24. Huber M, Beutler B, Keppler D. Tumor necrosis factor alpha stimulates leukotriene production in vivo. Eur J Immunol. 1988;18:2085–2088
  25. Lukacs NW, Strieter RM, Chensue SW, Widmer M, Kunkel SL. TNF-alpha mediates recruitment of neutrophils and eosinophils during airway inflammation. J Immunol. 1995;154:5411–5417
  26. Slungaard A, Vercellotti GM, Walker G, Nelson RD, Jacob HS. Tumor necrosis factor alpha/cachectin stimulates eosinophil oxidant production and toxicity towards human endothelium. J Exp Med. 1990;171:2025–2041
  27. Scheurich P, Thoma B, Ucer U, Pfizenmaier K. Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNF-alpha-mediated enhancement of T cell responses. J Immunol. 1987;138:1786–1790
  28. Lassalle P, Delneste Y, Gosset P, Tonnel AB, Capron A. Potential implication of endothelial cells in bronchial asthma. Int Arch Allergy Appl Immunol. 1991;94:233–238
  29. Walter MJ, Morton JD, Kajiwara N, Agapov E, Holtzman MJ. Viral induction of a chronic asthma phenotype and genetic segregation from the acute response. J Clin Invest. 2002;110:165–175
  30. Franchimont D, Martens H, Hagelstein MY, Louis E, Dewe W, Chrousos GP, et al. Tumor necrosis factor alpha decreases, and interleukin-10 increases, the sensitivity of human monocytes to dexamethasone: potential regulation of the glucocorticoid receptor. J Clin Endocrinol Metab. 1999;84:2834–2839
  31. Amrani Y, Panettieri RA, Frossard N, Bronner C. Activation of the TNF alpha-p55 receptor induces myocyte proliferation and modulates agonist-evoked calcium transients in cultured human tracheal smooth muscle cells. Am J Respir Cell Mol Biol. 1996;15:55–63
  32. Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G. Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol. 1993;122:103–111
  33. Sullivan DE, Ferris M, Pociask D, Brody AR. Tumor necrosis factor-alpha induces transforming growth factor-beta1 expression in lung fibroblasts through the extracellular signal-regulated kinase pathway. Am J Respir Cell Mol Biol. 2005;32:342–349
  34. 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
  35. Berger P, Girodet PO, Begueret H, Ousova O, Perng SW, Marthan R, et al. Tryptase-stimulated human airway smooth muscle cells induce cytokine synthesis and mast cell chemotaxis. FASEB J. 2003;17:2139–2141
  36. Brightling CE. Chronic cough due to nonasthmatic eosinophilic bronchitis: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(suppl):116S–121S
  37. 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
  38. Slats AM, Janssen K, van Schadewijk A, van der Plas DT, Schot R, van den Aardweg JG, et al. Bronchial inflammation and airway responses to deep inspiration in asthma and COPD. Am J Respir Crit Care Med. 2007;176:121–128
  39. Brightling CE, Symon FA, Birring SS, Bradding P, Wardlaw AJ, Pavord ID. Comparison of airway immunopathology of eosinophilic bronchitis and asthma. Thorax. 2003;58:528–532
  40. Brightling CE, Ward R, Goh KL, Wardlaw AJ, Pavord ID. Eosinophilic bronchitis is an important cause of chronic cough. Am J Respir Crit Care Med. 1999;161:406–410
  41. Brightling CE. Chronic cough due to nonasthmatic eosinophilic bronchitis: ACCP evidence-based clinical practice guidelines. Chest. 2006;129(suppl):116S–121S
  42. 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
  43. Chen FH, Samson KT, Miura K, Ueno K, Odajima Y, Shougo T, et al. Airway remodeling: a comparison between fatal and nonfatal asthma. J Asthma. 2004;41:631–638
  44. Pennings HJ, Kramer K, Bast A, Buurman WA, Wouters EF. Tumour necrosis factor-alpha induces hyperreactivity in tracheal smooth muscle of the guinea-pig in vitro. Eur Respir J. 1998;12:45–49
  45. Reynolds AM, Holmes MD, Scicchitano R. Cytokines enhance airway smooth muscle contractility in response to acetylcholine and neurokinin A. Respirology. 2000;5:153–160
  46. Chen H, Tliba O, Van Besien CR, Panettieri RA, Amrani Y. Selected contribution: TNF-α modulates murine tracheal rings responsiveness to G-protein-coupled receptor agonists and KCl. J Appl Physiol. 2003;95:864–872
  47. Zhang Y, Adner M, Cardell LO. Up-regulation of bradykinin receptors in a murine in-vitro model of chronic airway inflammation. Eur J Pharmacol. 2004;489:117–126
  48. Adner M, Rose AC, Zhang Y, Sward K, Benson M, Uddman R, et al. An assay to evaluate the long-term effects of inflammatory mediators on murine airway smooth muscle: evidence that TNFalpha up-regulates 5-HT(2A)-mediated contraction. Br J Pharmacol. 2002;137:971–982
  49. Sukkar MB, Hughes JM, Armour CL, Johnson PR. Tumour necrosis factor-alpha potentiates contraction of human bronchus in vitro. Respirology. 2001;6:199–203
  50. Anticevich SZ, Hughes JM, Black JL, Armour CL. Induction of human airway hyperresponsiveness by tumour necrosis factor-alpha. Eur J Pharmacol. 1995;284:221–225
  51. Amrani Y, Bronner C. Tumor necrosis factor alpha potentiates the increase in cytosolic free calcium induced by bradykinin in guinea-pig tracheal smooth muscle cells. C R Acad Sci III. 1993;316:1489–1494
  52. Amrani Y. Airway smooth muscle modulation and airway-hyperresponsiveness in asthma: new cellular and molecular paradigms. Exp Rev Clin Immunol. 2006;2:353–364
  53. Amrani Y, Panettieri RA. Modulation of calcium homeostasis as a mechanism for altering smooth muscle responsiveness in asthma. Curr Opin Allergy Clin Immunol. 2002;2:39–45
  54. Hunter I, Cobban HJ, Vandenabeele P, MacEwan DJ, Nixon GF. Tumor necrosis factor-alpha-induced activation of RhoA in airway smooth muscle cells: role in the Ca(2+) sensitization of myosin light chain(20) phosphorylation. Mol Pharmacol. 2003;63:714–721
  55. Deshpande DA, Walseth TF, Panettieri RA, Kannan MS. CD38-cyclic ADP-ribose-mediated Ca2+ signaling contributes to airway smooth muscle hyperresponsiveness. FASEB J. 2003;17:452–454
  56. Deshpande DA, White TA, Dogan S, Walseth TF, Panettieri RA, Kannan MS. CD38/cyclic ADP-ribose signaling: role in the regulation of calcium homeostasis in airway smooth muscle. Am J Physiol Lung Cell Mol Physiol. 2005;288:L773–L788
  57. Tliba O, Panettieri RA, Tliba S, Walseth TF, Amrani Y. Tumor necrosis factor-alpha differentially regulates the expression of proinflammatory genes in human airway smooth muscle cells by activation of interferon-beta-dependent CD38 pathway. Mol Pharmacol. 2004;66:322–329
  58. Tliba O, Tliba S, Da Huang C, Hoffman RK, DeLong P, Panettieri RA, et al. Tumor necrosis factor α modulates airway smooth muscle function via the autocrine action of interferon β. J Biol Chem. 2003;278:50615–50623
  59. Erin EM, Leaker BR, Nicholson GC, Tan AJ, Green LM, Neighbour H, 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
  60. Rouhani FN, Meitin CA, Kaler M, Miskinis-Hilligoss D, Stylianou M, Levine SJ. Effect of tumor necrosis factor antagonism on allergen-mediated asthmatic airway inflammation. Respir Med. 2005;99:1175–1182
  61. Morjaria JB, Chauhan AJ, Bobu KS, Mehta RL, Smith S, North M, et al. Assessment of a soluble TNFalpha receptor fusion protein (etanercept) as a novel therapeutic agent for severe refractory asthma. [abstract] Proc Am Thorac Soc. 2006;3:A16
  62. Rennard SI, Fogarty C, Kelsen S, Long W, Ramsdell J, Allison J, et al. On behalf of the COPD investigators: The safety and efficacy of infliximab in moderate to severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;175:926–934

 (Supported by an unrestricted educational grant from Genentech, Inc. and Novartis Pharmaceuticals Corporation)

 Series editors: Donald Y. M. Leung, MD, PhD, and Dennis K. Ledford, MD

 Supported by Asthma UK, a DOH Clinician Scientist award, and NIH06364.

 Disclosure of potential conflict of interest: C. Brightling has consulting arrangements with Cambridge Antibody Technology, GlaxoSmithKline, AstraZeneca, Pfizer, Roche, and Piramed; owns stock in Leicester AIR; has received grant support from AstraZeneca, Cambridge Antibody Technology, and GlaxoSmithKline; and is on the speakers' bureau for AstraZeneca and GlaxoSmithKline. Y. Amrani has received grant support from Centocor and the National Institutes of Health. M. Berry has declared that he has no conflict of interest.

PII: S0091-6749(07)01999-9

doi: 10.1016/j.jaci.2007.10.028

The Journal of Allergy and Clinical Immunology
Volume 121, Issue 1 , Pages 5-10 , January 2008

Article Tools

* Image Usage & Resolution