Features of cytokine signaling forming T-helper immune response in COPD of varying severity

Introduction — Currently, chronic obstructive pulmonary disease (COPD) is a global public health problem. However, molecular mechanisms of the development of this pathology are still poorly understood. The aim is to establish mechanisms of cytokine regulation of T-helper (Th) immune pathway in patients with COPD of varying severity. Material and Methods — The study included 112 patients with stable COPD (mild, moderate and severe grade) and 32 healthy volunteers (control group). We investigated serum cytokine levels (tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin 4 (IL-4), IL-6, IL-10, IL-17A) and the percentage of circulating Th cells (CD4+) expressing membrane receptor to IL-6 (IL-6R or CD126+), using flow cytometry. The levels of transforming growth factor-β1 (TGF-β1) and IL-21 were detected by ELISA. The direction of immune response in COPD patients was determined depending on the prevalence of cytokines playing a crucial role in the formation of certain Th cells type (Th1, Th17). Results — Th1-associated cytokine profile was expressed at the initial stage of COPD; the Th17-associated cytokine profile begins to prevail at severe COPD. Among COPD patients with Th1-associated cytokine profile, a statistically significant increase in the number of CD4+CD126+ cells in comparison with the control group was identified only in severe COPD. In the group of COPD patients with Th17-associated cytokine profile, an increase in the number of CD4+CD126+ cells were observed at all severity stages of the pathology. Conclusion — Moderate and severe COPD are characterized by the predominance of Th17-associated cytokine profile leading to chronic inflammation. The increase in IL-6R expression levels in circulating CD4+ cells serves as the mechanism for enhancing Th17-associated response in COPD.