Immunological pathways in virus-induced COPD exacerbations: a role for IL-15.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by high levels of antiviral type 1 cytokine interferon-γ and activated CD8(+) T cells. COPD exacerbations are the major cause of morbidity and mortality, have a prolonged and intense effect on quality of life and may result in accelerated loss of lung function. Respiratory virus infections, frequently within a state of colonization by bacteria, are the major cause of COPD exacerbations, and there is also evidence of virus latency in 'stable' disease, suggesting that latent infection might be a cause of chronic inflammation in COPD.

Design: This is an update of current literature concerning the role of interleukin-15 and major histocompatibility complex class I-related chain A and B molecules in type 1 immune responses, particularly to respiratory virus infections, which are the main cause of COPD exacerbations. We also present data from our own group suggesting a role for interleukin-15 in virus-induced COPD exacerbations.

Results: Type 1 cytokine interleukin-15 is produced by resident airway cells (epithelial cells and macrophages) in response to virus infection and bacteria. Virus infections modulate major histocompatibility complex class I-related chain A and B molecules in respiratory epithelial cells.

Conclusions: Interleukin-15 could play a major role in the airway inflammation in COPD directly, via its own receptors, by amplifying the type 1 immune responses and decreasing apoptosis or indirectly, via modulating molecules associated with cytotoxic activity of natural killer and CD8(+) T cells, such as major histocompatibility complex class I-related chain A and B.