Increased innate and adaptive immune responses in induced sputum of young smokers.

BACKGROUND AND OBJECTIVES: It is known that chronic obstructive pulmonary disease (COPD) development process is imperceptible and can be asymptomatic for 20 or more years. It is of great importance to diagnose early inflammatory changes that can lead to COPD in young asymptomatic cigarette smokers. The aim of our study was to analyze the cell spectrum of induced sputum (IS) of young cigarette smokers, with emphasis on T-regulatory cells. MATERIALS AND METHODS: A total of 20 healthy nonallergic smokers, 20 nonsmokers and 20 COPD patients were enrolled in the study. After lung function measurements were taken, we performed sputum induction and analyzed sputum cells. We evaluated the cell count of FOXP3-positive, CD4+ and CD8+ T lymphocytes by immunocytochemistry staining, and the cell count of macrophages and neutrophils by May-Grünwald Giemsa staining. RESULTS: Induced sputum of smokers contained a higher absolute amount of macrophages and neutrophils when compared to nonsmokers. FOXP3-positive cells in the sputum of young smokers showed a statistically significant increase when compared to nonsmokers. Induced sputum of COPD patients contained an increased absolute amount of neutrophils and FOXP3-positive Treg cells when compared to nonsmokers. Regression analysis showed that the amount of FOXP-3 positive cells, neutrophils and macrophages in the induced sputum was increasing with the number of pack years. CONCLUSIONS: This study demonstrates that young smokers have early inflammatory changes in their airways that not only initiate nonspecific mechanisms recruiting neutrophils, but also involve specific immune mechanisms with recruitment of T regulatory lymphocytes. The lymphocyte response is probably adaptive.

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 B(4) (LtB(4)) to the synthesis of anti-inflammatory lipoxins plays an important role. The aim of our study was to determine the content of lipoxin A(4) (LXA(4)) and LtB(4) 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 LXA(4) and LtB(4) content and inflammatory cell spectrum. RESULTS: COPD patients had a significantly lower sputum LXA(4) concentration and LtB(4)/LXA(4) ratio compared with healthy controls. A significant negative correlation was found between the LXA(4) concentration and the relative neutrophil count and between the LtB(4)/LXA(4) ratio and the relative macrophage count. CONCLUSIONS: COPD patients during the late phase of exacerbation had a suppressed production of LXA(4) and an elevated LtB(4)/LXA(4) 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.

Relation of inflammatory chemokines to insulin resistance and hypoadiponectinemia in coronary artery disease patients.

BACKGROUND: Although many studies have shown that the metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) both are associated with chronic inflammatory state and are risk factors for coronary artery disease (CAD), it is still unclear which condition is a more important contributor to the increased production of inflammatory chemokines. The purpose of this study was to assess monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) levels and their association with insulin resistance and adiponectin concentrations in CAD patients, who were categorized as having T2DM, MS, or neither. METHODS: CAD male patients were categorized into three groups: 24 non-obese patients with T2DM (D), 24 obese patients with MS (M) and 24 patients without T2DM or MS (W). 20 healthy subjects were selected as controls (C). Insulin resistance was assessed by the HOMA-IR method, but serum MCP-1, IL-8, and adiponectin levels were measured by xMAP technology. RESULTS: Serum levels of MCP-1 and IL-8 in D and M groups were increased in comparison with W and C groups (p<0.001, p<0.01), but the increase in the M group was significantly higher than that in the D group (p<0.05, p<0,001), besides MCP-1 and IL-8 concentrations were correlated with HOMA-IR indexes (r=0.52; r=0.49, p<0.0001) and adiponectin levels (r=-0.59, p<0.0001). The M group demonstrated a diminution in the adiponectin level (p<0.01) and pronounced increase of HOMA-IR in comparison with the other three groups (p<0.01). CONCLUSION: Obese CAD patients with MS have a more pronounced increase of MCP-1, IL-8 and HOMA-IR and more decreased adiponectin levels than non-obese CAD patients without MS.