Th1, Th2 cytokines in airway response to acute cold exposure in patients with bronchial asthma

Abstract

Introduction. The concept of the interaction of multidirectional cytokines that control the cellular and humoral immune response in the cold bronchospasm in asthma has been little studied.Aim. To evaluate the role of Th1 and Th2 cytokines in the formation of the airway response to a cold stimulus in patients with asthma.Materials and methods. The spectrum of cytokines (IFN-γ, IL-17А, TNFα, IL-1β, IL-2, IL-6, IL-4), protein IP-10 (chemokine CXCL10), MMP9 metalloproteinase and TIMP1 protein in exhaled breath condensate before and after 3-minute isocapnic hyperventilation with cold (-20ºС) air (IHCA) has been studied in 37 patients.Results. Patients were divided into two groups: group 1 (n=11) consisted of individuals with cold airway hyperresponsiveness (CAHR), group 2 – 26 individuals with no response to IHCA (ΔFEV1 IHCA = -16.5±2.3 and -1.5±0.85%, respectively, p<0.0001). Pro-inflammatory cytokines TNFα, IL-2, IL-1β, and IL-6 had a predominant effect on the development of CAHR. IFN-γ was considered as a central regulator of the bronchial response to a cold stimulus, the increase in the level of which in cold bronchospasm relative to the group without CAHR (399,52 [237,1; 753,23] and 237,99 [57,63; 304,84] fg/mL, respectively, p<0.05) was accompanied by an increase in the concentration of IFN-γ-induced protein IP-10 (201.12 [199.4; 398.81] and 167.33 [132.94; 212.77] fg/mL, respectively (p<0.05). The absence of dynamics of IL-4 concentration in response to IHCA testified to the minimal involvement of IL-4 in the implementation of CAHR. The involvement of IL-17A could be associated with the activity of Th1 cytokines and the cold-activated proteolysis-antiproteolysis system involved in bronchial remodeling ‒ metalloproteinase MMP9 and a specific inhibitor of metalloproteinases TIMP1, the values of the latter two were higher in individuals with CAHR after the IHCA test.Conclusion. In patients with asthma, in the implementation of cold bronchospasm, the dominance of the Th1 immune response and a decrease in the functional activity of Th2 cytokines are observed.