Immunmodulatorische Therapie bei allergischem Asthma

Zusammenfassung

Das allergische Asthma ist eine immunologische Erkrankung, die durch entzündliche Veränderungen charakterisiert ist. Unterschiedliche Ansätze der Immunmodulation sind für die Erkrankung entwickelt worden. Bisher zugelassen und klinisch erfolgreich angewendet für die Behandlung werden die spezifische Immuntherapie SIT und die Gabe von monoklonalen Antikörper gegen IgE. Weitere Ansätze wie eine Modulation von T-Zellen, Hemmung von Effektorzytokinen oder Zellmigration sowie mikrobielle Adjuvantien sind sehr interessant, befinden sich aber meist noch im experimentellen Stadium.

Summary

Allergic asthma is an immunological disease characterized by certain inflammatory changes in the airways and the lung. Different approaches for immune modulation have been developed to treat this disease. Clinical approved immune modulators include the specific immune therapy (SIT) and treatment with monoclonal antibodies against IgE. Further approaches, like inhibition or modulation of T cell responses, inhibition of effector cytokines or inhibition of cell migration are very interesting but still in development and so far not established for treatment of patients.

Schlüsselwörter

Immunmodulation - Asthma bronchiale - spezifische Immuntherapie

Key words

immune modulation - asthma - specific immunotherapy

Literatur

• 1 Abramson M J, Puy R M, Weiner J M. Allergen immunotherapy for asthma.  Cochrane Database Syst Rev. 2003;  , CD001186
• 2 Beeh K M, Beier J, Meyer M. et al . Bimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics: a randomized, double-blind, placebo-controlled clinical cross-over-trial.  Pulm Pharmacol Ther. 2006;  19 233-41
• 3 Beier K C, Kallinich T, Hamelmann E. T-cell co-stimulatory molecules: novel targets for the treatment of allergic airway disease.  Eur Respir J. 2007;  30 383-90
• 4 Berry M A, Hargadon B, Shelley M. et al . Evidence of a role of tumor necrosis factor alpha in refractory asthma.  N Engl J Med. 2006;  354 697-708
• 5 Bousquet J, Cabrera P, Berkman N. et al . The effect of treatment with omalizumab, an anti-IgE antibody, on asthma exacerbations and emergency medical visits in patients with severe persistent asthma.  Allergy. 2005;  60 302-8
• 6 Broide D H. Immunostimulatory sequences of DNA and conjugates in the treatment of allergic rhinitis.  Curr Allergy Asthma Rep. 2005;  5 182-5
• 7 Buhl R, Beeh K M. Spezifische Immuntherapie bei allergischem Asthma bronchiale?.  Pneumologie. 2003;  57 69-70
• 8 Buhl R, Berdel D, Criee C P. et al . Leitlinie zur Diagnostik und Therapie von Patienten mit Asthma.  Pneumologie. 2006;  60 139-77
• 9 Buhl R, Soler M, Matz J. et al . Omalizumab provides long-term control in patients with moderate-to-severe allergic asthma.  Eur Respir J. 2002;  20 73-8
• 10 Erb K J. Helminths, allergic disorders and IgE-mediated immune responses: where do we stand?.  Eur J Immunol. 2007;  37 1170-3
• 11 Erin E M, Leaker B R, Nicholson G C. et al . The effects of a monoclonal antibody directed against tumor necrosis factor-alpha in asthma.  Am J Respir Crit Care Med. 2006;  174 753-62
• 12 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 1029-36
• 13 Francis J N, Durham S R. Adjuvants for allergen immunotherapy: experimental results and clinical perspectives.  Curr Opin Allergy Clin Immunol. 2004;  4 543-8
• 14 Garn H, Mittermann I, Valenta R, Renz H. Autosensitization as a pathomechanism in asthma.  Ann N Y Acad Sci. 2007;  1107 417-25
• 15 Gauvreau G M, Becker A B, Boulet L P. et al . The effects of an anti-CD11a mAb, efalizumab, on allergen-induced airway responses and airway inflammation in subjects with atopic asthma.  J Allergy Clin Immunol. 2003;  112 331-8
• 16 Gauvreau G M, Hessel E M, Boulet L P. et al . Immunostimulatory sequences regulate interferon-inducible genes but not allergic airway responses.  Am J Respir Crit Care Med. 2006;  174 15-20
• 17 Hansen G, Berry G, DeKruyff R H, Umetsu D T. Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation.  J Clin Invest. 1999;  103 175-83
• 18 Horner A A, Raz E. Immunostimulatory sequence oligodeoxynucleotide-based vaccination and immunomodulation: two unique but complementary strategies for the treatment of allergic diseases.  J Allergy Clin Immunol. 2002;  110 706-12
• 19 Jacobsen L, Niggemann B, Dreborg S. et al . Specific immunotherapy has long-term preventive effect of seasonal and perennial asthma: 10-year follow-up on the PAT study.  Allergy. 2007;  62 943-8
• 20 Kon O M, Sihra B S, Loh L C. et al . The effects of an anti-CD4 monoclonal antibody, keliximab, on peripheral blood CD4+ T-cells in asthma.  Eur Respir J. 2001;  18 45-52
• 21 Korn S, Günther C, Taube C, Buhl R. Anti-interleukin-5 therapy for hypereosinophilic asthma.  Am J Respir Crit Care Med. 2007;  175 A486
• 22 Kroczek R, Hamelmann E. T-cell costimulatory molecules: optimal targets for the treatment of allergic airway disease with monoclonal antibodies.  J Allergy Clin Immunol. 2005;  116 906-9
• 23 Kuehr J, Brauburger J, Zielen S. 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. 2002;  109 274-80
• 24 Leckie M J, ten B rinke 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 2144-8
• 25 Mortimer K, Brown A, Feary J. et al . Dose-ranging study for trials of therapeutic infection with Necator americanus in humans.  Am J Trop Med Hyg. 2006;  75 914-20
• 26 Noga O, Hanf G, Brachmann I. et al . Effect of omalizumab treatment on peripheral eosinophil and T-lymphocyte function in patients with allergic asthma.  J Allergy Clin Immunol. 2006;  117 1493-9
• 27 Palmqvist C, Wardlaw A J, Bradding P. Chemokines and their receptors as potential targets for the treatment of asthma.  Br J Pharmacol. 2007;  151 725-36
• 28 Simon H U, Seelbach H, Ehmann R, Schmitz M. Clinical and immunological effects of low-dose IFN-alpha treatment in patients with corticosteroid-resistant asthma.  Allergy. 2003;  58 1250-5
• 29 Soler M, Matz J, Townley R. et al . The anti-IgE antibody omalizumab reduces exacerbations and steroid requirement in allergic asthmatics.  Eur Respir J. 2001;  18 254-61
• 30 Summers R W, Elliott D E, Urban Jr J F. et al . Trichuris suis therapy in Crohn’s disease.  Gut. 2005;  54 87-90
• 31 Taube C, Duez C, Cui Z H. et al . The role of IL-13 in established allergic airway disease.  J Immunol. 2002;  169 6482-9
• 32 Trujillo-Vargas C M, Werner-Klein M, Wohlleben G. et al . Helminth-derived products inhibit the development of allergic responses in mice.  Am J Respir Crit Care Med. 2007;  175 336-44
• 33 Wenzel S, Wilbraham D, Fuller R. et al . 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 1422-31
• 34 Yazdanbakhsh M, Kremsner P G, RR. Allergy, parasites, and the hygiene hypothesis.  Science. 2002;  296 490-4