Asthma has been classified into different subgroups, such as the Th2-type (atopic) or non-atopic type, based on allergen-specific IgE levels and blood eosinophil counts. These subgroups, named as endotypes, can potentially be based on the pathophysiological differences. For instance, Th2-type cytokines been proven to play pivotal roles in atopic asthma, whereas IL-17A might be involved in severe refractory asthma.
In this study, we investigated the serum levels of cytokines and chemokines in relation to asthmatic disease severity. We measured serum levels of twenty-four cytokines and chemokines in healthy controls (n=34) and asthmatic patients (n=77). The serum levels were also compared among patient groups with different disease activities and characteristics.
Interestingly, the levels of nine cytokines were significantly higher in asthmatic patients than in controls, and the levels of IL-17A and SCF were significantly different between uncontrolled and well-controlled patient groups (p=0.003). IL-17A levels were significantly correlated with those of IL-4, IL-25, IL-9, IL-10 and IFN-g in uncontrolled asthmatic patients. Moreover, the patients with very high levels of these cytokines exhibited refractoriness to a high-dose of inhaled corticosteroid therapy, and had a history of acute exacerbation within one year, which necessitated systemic steroid therapy.
This study showed various asthmatic endotypes, including TH2 and TH17 types. In addition, we revealed a significant correlation between serum IL-17A levels and severity of asthma, and identified a group of severe refractory patients with up-regulation of both IL-17A and Th2-type cytokines.
Our multi-serum cytokine analysis suggests the classification of multiple inflammatory endotypes, leading to the selection of optimal therapies.