Relationship of Serum Levels of IL-17, IL-18, TNF-α, and Lung Function Parameters in Patients with COPD, Asthma-COPD Overlap, and Bronchial Asthma

Abstract

Determination of markers of systemic inflammation is one of the important directions in the study of pathogenesis and improvement of diagnosis of chronic obstructive pulmonary disease (COPD), asthma-COPD overlap (ACO), and bronchial asthma (BA). The aim of our work was a comparative study of the features of changes in serum levels of IL-17, IL-18, and TNF-α in patients with COPD, ACO, and BA with various severity of the disease, as well as evaluation of the relationship between the level of these cytokines and lung ventilation function. A total of 147 patients with COPD (n=58), ACO (n=57), and BA (n=32) during a stable period have been examined in this study. The control group included 21 healthy nonsmokers with similar sex-age indicators. Serum levels of IL-17, IL-18, and TNF-α were determined by ELISA. The concentrations of these cytokines in the circulation in the studied patients with COPD, ACO, and BA were higher than those in healthy nonsmokers (p≤0.001). IL-17 and IL-18 levels in the blood serum were comparable in all examined patients. The mean TNF-α concentrations in the circulation in COPD and ACO were significantly higher than those in BA (p<0.001). In patients with COPD, the levels of IL-17 and TNF-α increased progressively against the background of a decrease in numerous spirometric indicators, which allows us to consider these cytokines as systemic biomarkers of disease severity. In BA, the inverse correlations between the level of IL-17 and FEV1/FVC (%) and FEV1 have been found. In patients with ACO, the increase in IL-18 levels was associated with a decrease in FEV1 and TNF-α with FEV1/FVC (%). These findings indicate that IL-17, IL-18, and TNF-α can participate in the mechanisms of systemic inflammation and the genesis of disorders of airway obstruction in COPD, AСO, and BA. An increase in the levels of IL-17 and TNF-α may be associated with impaired bronchial patency in COPD and BA. The established associations of the IL-18 concentration in the blood serum and FEV1 only in patients with ACO allow using the level of IL-18 as a potential marker of the degree of impaired airway obstruction in this disease.

MiR‐221‐3p and miR‐92a‐3p enhances smoking‐induced inflammation in COPD

“… 26 In this study, we observed that 16HBECs after CSE treatment were predisposed to apoptosis (Figure 4C ), and they produced larger amounts of inflammatory cytokines, including TNF‐α, IL‐6, IL‐1β, and TGF‐β1, and airway remodeling biomarkers, including Collagen IV, Fibronectin and α‐SMA, than 16HBECs treated by none (Figure 4D–E ), which implied that airway epithelium might be injured by CSE. Regarding inflammatory factors investigated here, TNF‐α and IL‐1βare up‐regulated when inflammation cascade is initiated, 27 , 28 and IL‐6 level, mainly secreted by monocytes and macrophages, is prominently increased as inflammation severity of COPD escalates. 29 TGF‐β1, released by monocytes, expedites airway remodeling by promoting proliferation of airway smooth muscle cells, 30 which also explains why levels of airway remodeling biomarkers were increased in CSE‐exposed 16HBECs (Figure 4E ).…”

ACO (Asthma–COPD Overlap) Is Independent from COPD, a Case in Favor: A Systematic Review

“…These data suggest that neutrophilic inflammation, emphysematous changes and epithelial injuries might contribute to the elevated levels of NGAL in induced sputum from patients with ACO [ 128 ]. However, pro-inflammatory cytokines associated with type 1 and type 2 immunity in peripheral blood might not be useful to diagnose ACO from COPD [ 91 , 96 ].…”

Jagged2-γδT17 is Regulated by Mycobacterium Vaccae in Asthmatic Mice

“…Studies have also shown that allergic asthma can be alleviated by inhibiting IL-4R α-Stat6 and the Jagged1/Jagged2-Notch1/Notch2 signaling pathways in mice [11] . On the other hand, IL-17 exerts signi cant in uence in activating and recruiting neutrophils, enhancing in ammatory cell in ltration, participating in airway remodeling, and promoting airway hypertrophy [33][34][35][36] . γδT cells support the Th1/Th2 imbalance, implicating γδT cells in asthma development [3,37,38] .…”