Th17/Treg-related cytokine imbalance in sulfur mustard exposed and stable chronic obstructive pulmonary (COPD) patients: correlation with disease activity

Abstract

In this study, we investigated expression changes of Th17/Treg-related cytokine in transbronchial lung biopsy (TBLBs) of sulfur mustard (SM) exposure, stable chronic obstructive pulmonary disease (COPD) patients and also compared it with a healthy control (HC) group. Here, ROR-γt, FoxP3, and Treg/Th17-related cytokines (IL-10, IL-17A, IL-6, and TGF-β1) were assessed using a combination of RT–QPCR and ELISA in 11 SM-exposed cases, 9 patients with GOLD stage II COPD diagnosed, and 8 HC. Our results showed that the levels of Foxp3 expression were lower and ROR-γt expression was higher in SM and COPD patients when compared with HC (all p values were less than 0.001). The relative Foxp3 expressions and Foxp3/ROR-γt ratio were positively correlated with FEV1 (%) pred (R = 0.682 and R = 0.602, respectively; p ≤ 0.001). However, the relative ROR-γt expressions were inversely correlated with FEV1 (%) pred (R= −0.75, p = 0.003) and relative Foxp3 expression (R= −0.704, p = 0.003). The mRNA and protein expression of IL-10 were significantly decreased in SM and COPD patients compared with HC (p < 0.001). An increase of IL-17A (∼7.2 fold) and TGF-β1 (∼5.6 fold) are involved in the lung exacerbation of SM and COPD patients. The expression of IL-6 was variable between three groups (p ≥ 0.05). In addition, an inverse correlation were observed between FEV1 (%) pred and expressions of IL-17A (R= −0.741), IL-6 (R= −0.673) and TGF-β1 (R= −0.632) (p ≤ 0.001). Instead, positive correlation was found between IL-10 ratios and FEV1 (%) pred (R = 0.777, p = 0.001). These findings suggest that Treg/Th17-mediated distributions are involved in the progression of chronic lung injury of SM and COPD patients.