Virus-Induced Airway Inflammation
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Virus-Induced Airway Inflammation
Virus-induced cytokine production and inflammatory cell activation are instrumental in the development of neurogenic inflammatory responses, and these combined factors increase bronchoconstriction in response to allergens or irritants. Viral infections can influence both the development and the severity of asthma. In early life, viral infections can either increase or, remarkably, decrease the risk of subsequent asthma. In children and adults with existing asthma, viral respiratory infections frequently cause acute airway obstruction and wheezing.

The airway epithelium is the first cellular component of the lung to be encountered by the particles and pathogens present in inhaled air. Hence it is the focal point in the pathogenesis of viral respiratory infections because it serves as the host cell for viral replication, and it can also initiate innate immune responses. Damage to the epithelial cells can disturb airway physiology through several different pathways. For example, epithelial oedema and shedding, together with mucus production, can cause airway obstruction and wheezing. The immune response to the virus, including cell recruitment and activation, and secretion of pro-inflammatory cytokines and mediators (for example, leukotrienes, kinins, myeloperoxidase and prostenoids), can also contribute to the pathogenesis of respiratory infections. For viruses such as rhinoviruses, which infect relatively few cells in the airway, it may be the primary mechanism that causes airway symptoms and lower airway dysfunction (Ref.1). Following the initial viral replication in epithelial cells, large amounts of virus are released into airway secretions and, presumably, into the surrounding lung tissues. At this point, the mononuclear cells are activated by high titres of virus to secrete pro-inflammatory cytokines such as IL-1, IL-8 (Interleukins), TNF-Alpha (Tumor Necrosis Factor-Alpha) and IFN-Gamma (Interferon-Gamma). These cytokines in turn, activate other cells in the airway environment and are also potent inducers of adhesion molecule expression. Together with chemokines like CCL5 generated by epithelial cells, this response provides a potent stimulus for the recruitment of inflammatory cells, which consist principally of neutrophils and T-Cells. Lymphocytes are recruited into the upper and lower airways during the early stages of a viral respiratory infection, and innate and adaptive immune responses may limit the extent of infection and clear virus-infected epithelial cells (Ref.2).

Viral replication can affect cell-surface receptors, resulting in the initiation of immune responses. In addition to its role as a physical barrier, the immunological activity of the airway epithelium is an essential part of the pulmonary immune system. Pre-exposure of airway epithelial cells to bacterial lipopolysaccharides or a proteolytically active house dust mite allergen inhibit or enhance the level of cellular infection with respiratory syncytial virus and similarly alter virus-induced expression of the inflammatory chemokine IL-8 (Ref.3). Viral infections are a major cause of wheezing and exacerbations of asthma in all age groups and current treatment options are not very effective, impractical due to high cost or have significant side effects. The close epidemiological relationship between viral infections and wheezing indicates that more effective therapeutic strategies either to prevent certain viral infections or moderate the severity of these infections could have a major influence on the prevention or management of asthma.