The cytokine network in asthma and chronic obstructive pulmonary disease

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are very common inflammatory diseases of the airways. They both cause airway narrowing and are increasing in incidence throughout the world, imposing enormous burdens on health care. Cytokines play a key role in orchestrating the chronic inflammation and structural changes of the respiratory tract in both asthma and COPD and have become important targets for the development of new therapeutic strategies in these diseases. IntroductionThe most common inflammatory diseases of the airways are asthma and chronic obstructive pulmonary disease (COPD), and the incidence of both is increasing throughout the world. The prevalence of asthma in developed countries is approximately 10% in adults and even higher in children, whereas in developing countries, the prevalence is lower but increasing rapidly. The global prevalence of COPD is approximately 10% among individuals over the age of 40 years. Asthma often starts in early childhood and is characterized by intermittent wheezing and shortness of breath. In contrast, the predominant symptom in COPD is shortness of breath on exertion, which is persistent and slowly progressive. Although the clinical symptoms of both diseases are caused by airway narrowing as a result of inflammation in the airways, there are marked differences in the patterns of underlying inflammation.Cytokines play a key role in orchestrating the chronic inflammation of asthma and COPD by recruiting, activating, and promoting the survival of multiple inflammatory cells in the respiratory tract (Figure 1, Figure 2, and Table 1). Over 50 cytokines have now been identified in asthma and COPD, but their role in the pathophysiology of these complex airway diseases is often unclear. For the purpose of this Review, cytokines are classified into lymphokines (cytokines that are secreted by T cells and regulate immune responses), proinflammatory cytokines (cytokines that amplify and perpetuate the inflammatory process), growth factors (cytokines that promote cell survival and result in structural changes in the airways), chemokines (cytokines that are chemotactic for inflammatory cells), and antiinflammatory cytokines (cytokines that negatively modulate the inflammatory response), although many of these functions may overlap. Where possible, I have focused on human studies and have emphasized any therapeutic interventions that have been made.

Interleukin-31 promotes helper T cell type-2 inflammation in children with allergic rhinitis

“…IL-8 is a potent neutrophil chemoattractant and activator of neutrophils and is produced by a number of airway inflammatory cells, including neutrophils (18). Besides, IL-6 plays important role in asthma, especially in neutrophil infiltration (19). VEGF, previously known as vascular permeability factor, is the most specific growth factor for vascular endothelium (20).…”

IL13 activates autophagy to regulate secretion in airway epithelial cells

“…7,8 The actions of cytokines in the lung are widely investigated because of the interface of the airway with the environment, the susceptibility of the lung to infection, and the burden of chronic inflammatory airway diseases, particularly asthma and chronic obstructive pulmonary disease (COPD). 9,10 As an experimental model, the lung is ideal for the study of inflammatory responses due to the ease of direct delivery of cytokines to the airway in vivo and the ability to assay cultured primary airway epithelial cells in vitro. Using approaches similar to these, our group has recently demonstrated that airway epithelial cell IL33 (interleukin 33) leads to IL13 production and lung pathology in a mouse model and in cells obtained from patients with COPD.…”

PDE4-inhibitors: A novel, targeted therapy for obstructive airways disease

“…The major cause of COPD is cigarette smoking, although other environmental pollutants may also serve as triggers in susceptible individuals. These insults induce chronic inflammation and remodeling, including structural changes and destruction of alveolar tissue, within the lung [2][3][4][5].…”

“…The key effector cells within the airway tissue of COPD patients include macrophages, CD8+ T lymphocytes and neutrophils, releasing toxic mediators [2,5]. The destruction of alveolar tissue (emphysema) is thought to be caused by the release of proteinase (such as matrix metalloproteinase from alveolar macrophages) or as a consequence of an autoimmune response (e.g.…”