Role of Toll-Like Receptor 2 in Regulation of T-Helper Immune Response in Chronic Obstructive Pulmonary Disease.

Objective: According to modern views, the differences in the clinical course of chronic obstructive pulmonary disease (COPD) are associated with certain types of T-helper (Th) immune response. Recent data have shown that toll-like receptor 2 (TLR2) is involved in the development of Th immune response. However, TLR2-mediated regulation of Th subpopulation balance in COPD needs to be elucidated. The aim of our work is to determine the mechanisms of TLR2-mediated regulation of Th immune response in COPD of varying severity. Methods: The study included 323 smokers/ex-smokers with stable COPD (GOLD I, GOLD II, and GOLD III) and 97 healthy nonsmokers (control group). Serum levels of Th1 (TNF-α and IFN-γ), Th2 (IL-4), Th17 (IL-6 and IL-17A), Treg (IL-10) cytokines, and the percentage of peripheral blood Th cells expressing TLR2 (CD4+CD282+) were assessed by flow cytometry. Serum concentrations of IL-21 (Th17) and TGF-ß1 (Treg) were measured using the ELISA method. The predominant Th cytokine profile in serum was determined by calculating the ratios between levels of Th1 and Th17 cytokines. Spearman's correlation test was performed. Results: Patients with COPD GOLD II and III with Th1 and Th17 cytokine profiles exhibited an increase in the percentage of CD4+CD282+ cells compared to the control group. In COPD GOLD I-III, positive correlations between CD4+CD282+ cell frequency and Th17 cytokine levels (IL-6, IL-17A, and IL-21) were found. In COPD GOLD I, IL-10 concentration was negatively correlated with the percentages of studied cells; in COPD GOLD II, a positive correlation between these parameters was noted. Conclusions: Enhanced TLR2 expression on CD4+ cells shifts cytokine profile toward Th17 phenotype that plays a crucial role in COPD progression. The level of TLR2 expression on peripheral blood CD4+ cells may be considered as a biomarker for diagnosing and predicting the progression of COPD.

Impact evaluation of environmental factors on respiratory function of asthma patients living in urban territory.

BACKGROUND: Environmental pollution, local climatic conditions and their association with the prevalence and exacerbation of asthma are topics of intense current medical investigation. MATERIALS AND METHODS: Air pollution in the area of Vladivostock was estimated both by the index of emission volumes of "air gaseous components" (nitrogen oxide and nitrogen dioxide, formaldehyde, hydrogen sulfide, carbon monoxide) in urban atmosphere and by mass spectrometric analysis of precipitates in snow samples. A total of 172 local asthma patients (101 controlled-asthma patients-CAP and 71 non-controlled asthma patients - nCAP) were evaluated with the use of spirometry and body plethysmography. Airway obstruction reversibility was evaluated with the use of an inhaled bronchodilator. Using discriminant analysis the association of environmental parameters with clinical indices of asthma patients is explored and thresholds of impact are established. RESULTS: CAP presented high sensitivity to large-size suspended air particles and to several of the studied climatic parameters. Discriminant analysis showed high values of Wilks' lambda index (α = 0.69-0.81), which implies limited influence of environmental factors on the respiratory parameters of CAP. nCAP were more sensitive and susceptible to the majority of the environmental factors studied, including air suspended toxic metals particles (Cr, Zn and Ni). Air suspended particles showed higher tendency for pathogenicity in nCAP population than in the CAP, with a wider range of particle sizes being involved. Dust fractions ranging from 0 to 1 µm and from 50 to 100 µm were additionally implicated compared to CAP group. Considerably lowest thresholds levels of impact are calculated for nCAP.