Interleukin-33 Promotes Th2/Th17 Response in Eosinophilic and Non-Eosinophilic Nasal Polyps

BACKGROUND: Interleukin-33 (IL-33) is reported to be involved in Th2-skewed eosinophilic inflammation. A recent study also found that IL-33 exerted opposite effects on Th17 response in different diseases. However, the role of IL-33 in chronic rhinosinusitis with nasal polyps (NPs) was not explored. OBJECTIVES: The purpose of this study was to investigate the expression and function of IL-33 in chronic rhinosinusitis with NPs. MATERIALS AND METHODS: NP tissues from 60 NP patients and normal tissues of the inferior turbinate from 20 controls were sampled in operation. Immunochemistry was performed to identify eosinophilic or non-eosinophilic NPs. The expressions of IL-33 and Th1/2/17 cytokines were compared between different subtypes of NPs. The effect of IL-33 on Th response was detected in dispersed nasal polyp cells (DNPCs), and the signaling pathways involved in the process were detected using Western blot. RESULTS: The concentration of IL-33 was significantly elevated in both eosinophilic and non-eosinophilic NPs compared with controls. By in vitro study, we found that IL-33 can induce IL-4 and IL-5 production from eosinophilic DNPCs through the PI3K/AKT pathway, whereas IL-33 can induce IL-17 production from non-eosinophilic DNPCs through the ERK1/2 pathway. CONCLUSION: IL-33 is involved in Th2/Th17 response in NPs. Our study suggests that different types of NPs need a different treatment target.