Lipoxygenase-Derived Arachidonic Acid Metabolites in Chronic Obstructive Pulmonary Disease

Background and Objective. Chronic obstructive pulmonary disease (COPD) is characterized by a persistence of inflammation in large and small airways. We hypothesized that this could be caused by the inability of an inflammatory process to resolve. In the resolution of inflammation, a switching of arachidonic acid metabolism from the production of proinflammatory leukotriene B₄ (LtB₄) to the synthesis of anti-inflammatory lipoxins plays an important role. The aim of our study was to determine the content of lipoxin A₄ (LXA₄) and LtB₄ in induced sputum of patients with exacerbated COPD and to compare it to healthy controls, as well as to analyze the relationship between proinflammatory and anti-inflammatory mediators and an inflammatory cell spectrum in induced sputum.
Material and Methods. Induced sputum from 17 COPD patients and 7 healthy controls were analyzed for LXA₄ and LtB₄ content and inflammatory cell spectrum.
Results. COPD patients had a significantly lower sputum LXA₄ concentration and LtB₄/LXA₄ ratio compared with healthy controls. A significant negative correlation was found between the LXA₄ concentration and the relative neutrophil count and between the LtB₄/LXA₄ ratio and the relative macrophage count.
Conclusions. COPD patients during the late phase of exacerbation had a suppressed production of LXA4 and an elevated LtB₄/LXA₄ ratio in induced sputum demonstrating a proinflammatory imbalance. The correction of a balance between proinflammatory and anti-inflammatory eicosanoids by the administration of stable analogues of lipoxins could improve the treatment of chronic obstructive pulmonary disease in the future.