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

Abstract

Eur J Clin Invest 2012; 42 (9): 1010–1015 Abstract 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.

Severity of COPD and its relationship with IL-10

“…Regarding IL-15, it plays an important role in the antiviral immune response, contributing to the activation of survival cells and natural killer (NK) cells, CD8+, and NK T. Additionally, the hypertrophy of muscle fibers also favors and antagonizes muscle protein wasting, which can exert important influence in COPD, specially because patients with the disease usually have musculoskeletal dysfunction [44,45]. Studies investigating the role of IL-15 are limited among patients with COPD, but it is important to elucidate complications often exacerbated in some patients [46].…”

Acute exacerbations of chronic obstructive pulmonary disease are associated with decreased CD4+ & CD8+ T cells and increased growth & differentiation factor-15 (GDF-15) in peripheral blood

“…The elevation we demonstrated in serum IL-15 is significant due to its multiple actions that could potentiate lung inflammation during AE-COPD (reviewed in [ 56 ]). These include antigen-independent activation of CD8+ T cells and enhanced effector function of CD8+ T cells, NK cell and NK T cells.…”

Overproduction of growth differentiation factor 15 promotes human rhinovirus infection and virus-induced inflammation in the lung

“…Chronic obstructive pulmonary disease (COPD) affects more than 15.7 million adults and now is the third leading cause of death in the United States (58). Acute exacerbations of COPD lead to pronounced airway inflammation and accelerated lung function decline, which remarkably increases the morbidity, mortality, and substantial health care costs (66). Emerging evidence has shown that respiratory viral infection is the main cause of COPD exacerbations and linked to increased inflammatory cytokines (e.g., IL-6 and IL-8) and neutrophils in the lung during COPD exacerbations (1,5,22,29,36,42,43).…”