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Cytokines in asthma

Cytokines in astham review

Asthma is a chronic inflammatory disorder of the airways superimposed upon structural changes that include an increase in smooth muscle and airway wall remodeling. In addition to a background of chronic mediator release, asthma is characterized by consider-able variations in airway function brought about by important interactions with the environment, including allergen, pollutant and virus exposure. At least in mild–moderate disease, cytokines released from Th2 cells appear important in orchestrating the inflammation.

cytokines in astham

Cytokines in asthma

Asthma differs from other chronic inflammatory disorders, such as rheumatoid arthritis, Crohn's disease and psoriasis, in exhibiting a characteristic cytokine response dominated by Th2 cytokines, the majority of which are encoded in a small cluster on chromosome 5q32–34. It has been suggested that this coordinated regulation of the immune response in favor of Th2 cytokines, which include interleukin (IL)-3, IL-4, IL-5, IL-6, IL-9, IL-13 and granulocyte–macrophage colony stimulating factor (GM-CSF), results from a reduction in the inhibitory influence of Th1 cytokines, especially IL-18, IL-12 and interferon-γ, and, as a consequence, results in Th2 polarization of the immune response by default. This imbalance between Th1- and Th2-type immunity in those destined to become atopic manifests early in life, and possibly prenatally.

Clinical trials

Asthma is a chronic inflammatory disease of the airways and there are no preventions or cures. Inflammatory cells through the secretion of cytokines and pro-inflammatory molecules are thought to play a critical role in pathogenesis. Type 2 CD4+ lymphocytes (Th2 cells) and their cytokines predominate in mild to moderate allergic asthma, whereas severe steroid-resistant asthma has more of a mixed Th2/Th1 phenotype with a Th17 component. Other immune cells, particularly neutrophils, macrophages and dendritic cells, as well structural cells such as epithelial and airway smooth muscle cells also produce disease-associated cytokines in asthma. Increased levels of these immune cells and cytokines have been identified in clinical samples and their potential role in disease demonstrated in studies using mouse models of asthma. Clinical trials with inhibitors of cytokines such as interleukin (IL)-4, -5 and tumour necrosis factor- a have had success in some studies but not others. This may reflect the design of the clinical trials, including treatments regimes and the patient population included in these studies. IL-13, -9 and granulocyte-macrophage colony-stimulating factor are currently being evaluated in clinical trials or preclinically and the outcome of these studies is eagerly awaited. Roles for IL-25, -33, thymic stromal lymphopoietin, interferon- g, IL-17 and -27 in the regulation of asthma are just emerging, identifying new ways to treat inflammation. Careful interpretation of results from mouse studies will inform the development and application of therapeutic approaches for asthma. The most effective approaches may be combination therapies that suppress multiple cytokines and a range of redundant and disconnected pathways that separately contribute to asthma pathogenesis. Astute application of these approaches may eventually lead to the development of effective asthma therapeutics.(figure2)

role of cytokines in astham

Cytokines in asthma related reference

  1. 1, Peter J. Barnes, et al.Cytokine-directed therapies for asthma.J ALLERGY CLIN IMMUNOL VOLUME 108, NUMBER 2.
  2. 2,Paul M. O'Byrne, et al. Reassessing the Th2 cytokine basis of asthma.TRENDS in Pharmacological Sciences Vol.25 No.5 May 2004
  3. 3, Stephen T Holgate, et al.Cytokine and anti-cytokine therapy for the treatment of asthma and allergic disease.Allergology International(2004) 53:47–54
  4. 4, Heijmans-Antonissen C, Wesseldijk F, Munnikes RJ, et al.Cytokine/anti-cytokine therapy – novel treatments for asthma?.British Journal of Pharmacology (2011) 163 81–95
  5. 5, MASOUD MOVAHEDI, et al.IL-10, TGF-ß, IL-2, IL-12, and IFN- γ Cytokine Gene Polymorphisms in Asthma.Journal of Asthma, 45:790–794, 2008
  6. 6, PAUL S THOMAS, et al.Tumour necrosis factor- α : The role of this multifunctional cytokine in asthma.Immunology and Cell Biology (2001)79, 132–140

Cytokine molecules related

IL-1 Family

IL-1 Receptors

Other Interleukin

Other Interleukin Receptor

CSF Family

CSF Family Receptor

TNF family

TNF Receptor

Interferon (IFN)

IFN Receptor

IL6 Family

IL6 Receptor


Chemokine Receptor

More Cytokine molecules