Role of Cytokines in asthma
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.
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.
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.
Journal of Cytokine Biology