Treatment-recalcitrant chronic rhinosinusitis with polyps is associated with altered epithelial cell expression of interleukin-33

Background: Abnormalities in host mucosal immunity exist in chronic rhinosinusitis with nasal polyps (CRSwNPs), but it is unclear whether this is a cause or an effect of the eosinophilic inflammation and frequent microbial colonization that characterizes the disease Sinonasal epithelial cells (SNECs) are critical participants in healthy antimicrobial innate immune defense They also can promote Th2 inflammation with various mediators, including interleukin (IL)-33, which induces T helper cells to produce Th2 cytokines. Methods: CRSwNP SNECs were obtained during sinus surgery and stored Patients were subsequently classified as either treatment responsive or treatment recalcitrant, based on long-term outcomes of medical and surgical therapy Epithelial cells from these patients were grown in air liquid interface (ALI) culture and treated with IL-13, as well as the bacteria-associated molecule, CpG Expression of IL-33 mRNA was determined by real-tone polymerase chain reaction Results: Recalcitrant CRSwNP epithelial cells had increased baseline expression of IL-33 compared with responsive CRSwNPs, which was further increased by 24-hour exposure to CpG Treatment-responsive epithelial cells were not induced by CpG to express IL-33 Prolonged treatment with IL-73 during differentiation at the ALI diminished the baseline expression of IL-33 and prevented the subsequent induction of IL-33 by CpG Conclusion: Mucosal innate immunity likely plays an important role in CRSwNP pathogenesis A definitive link between infectious triggers and the development of Th2 inflammation has been elusive We have found constitutive IL-33 expression by SNECs in recalcitrant CRSwNPs, which can be furl her induced by a bacteria-associated molecular pattern Dysregulated epithelial cell immune interactions between host and environment may contribute to Th2 inflammation in CRSwNPs (Am J Rhinol Allergy 24, 105-109, 2010, doi 10.2500/ajra.2010.24.3446)