Interleukin-33 and thymic stromal lymphopoietin are primary cytokines involved in the Th1/Th2 inflammatory response in chronic secretory otitis media

Abstract

Background: T-helper (Th)1/Th2 inflammatory responses are responsible for secretory otitis media (SOM) development. However, the mechanisms underlying these immune responses remain unknown. This study aims to identify the primary cytokines that play essential roles in chronic SOM. Methods: Two groups were established for the present study: chronic SOM group ( n = 21) and control group ( n = 10). The middle ear effusion and serum samples of the expression cytokines (interleukin IL-2, IL-4, IL-5, IL-13, IL-17, IL-25, IL-33, interferon [IFN]-γ, thymic stromal lymphopoietin [TSLP], immunoglobulin IgE, and pepsins) were analyzed by enzyme-linked immunosorbent assay. Results: The levels of IL-4, IL-5, IL-13, IL-17, IL-25, IFN-γ, TLSP, pepsins, IL-2, and IL-33 (all, p < 0.001) were higher in middle ear effusion, when compared to those in serum, in chronic SOM group (non-paired sample). However, there was no significant difference in serum expression for those cytokines compared chronic SOM group and control group. The paired sample expression for IL-33 and TLSP (both, p = 0.046) were higher compared the effusion and serum in chronic SOM group. Conclusions: IL-33 produces inflammatory cytokines, such as IL-1b, IL-6, TNF-α, IL-10, IL-4, and TGF-β, which through nucleus into cytoplasm causing inflammatory responses. The present study revealed that IL-33 also produce IL-17, IL-4, IL-5, and IL-13 inflammatory factors, triggering an inflammatory response. Study reported that the combined stimulation of TSLP and IL-33 elicits an approximately 10-fold increase in cytokine production, when compared to the stimulation of IL-33 alone. This suggests that IL-33 and TLSP may be the primary cytokines involved in Th1/Th2 inflammatory responses in chronic SOM.