Increased serum IL-17A and Th2 cytokine levels in patients with severe uncontrolled asthma

Asthma is a syndrome of chronic bronchial inflammation and airway remodelling. Initially, asthma has been categorized into atopic and nonatopic types, based on antigen-specific IgE levels. Moreover, recently, asthma has been classified into different endotypes based on its pathophysiology, leading to the selection of the most optimal and effective therapies. Although T helper cell type 2 (Th2) cytokines were proven to play critical roles in atopic asthma, IL-17A has been reported to be involved in severe refractory asthma. In this study, we measured the levels of 24 cytokines/chemokines in the sera of healthy controls (HCs) (n = 34) and patients with asthma (n = 77), that were compared among patient groups with different disease activities and characteristics. The serum levels of nine cytokines were significantly higher in patients with asthma than in HCs, and the levels of IL-17A and SCF were significantly different between uncontrolled and well-controlled patient groups (p = 0.003). The IL-17A levels were significantly correlated with those of IL-4, IL-25, IL-10, and IFN-γ in patients with uncontrolled asthma, and the patients with the highest levels of all the above cytokines were refractory to high-dose of inhaled corticosteroid therapy and have a history of acute exacerbation within 1 year, requiring systemic steroid therapy. This study examines the profiles of upregulation and downregulation of various cytokines and chemokines in relation to asthmatic control status. IL-17A was significantly upregulated in patients with the uncontrolled and refractory status. Therefore, IL-17A may play important roles in asthmatic exacerbation, and its high level, in combination with upregulated Th2 and other cytokines, may indicate the refractory endotype of asthma.