Examining IL-33 expression in the cervix of HPV-infected patients: a preliminary study comparing IL-33 levels in different stages of disease and analyzing its potential association with IFN-γ

Research has shown the essential role of interleukin-33 (IL-33) in driving protective anti-viral immunity. IFN-gamma has been reported to improve IL-33 expression in cultured epithelial cells. The development of cervical intraepithelial neoplasia (CIN) and carcinogenesis was closely related to human papilloma virus (HPV) infection and defective anti-viral immunity. The aim of this study was to investigate IL-33 expression alternation during the disease progress and its association with IFN-gamma in HPV-positive patients. IL-33 was detected in endothelial cells and populations of epithelial cells in cervix. Though there was no statistically significant difference of IL-33 levels in cervical lavage and serum among different stages of disease (P > 0.05), the IL-33 protein and mRNA levels in cervical tissues were significantly lower in severe CIN patients than that of mild CIN or no CIN patients (P < 0.05). In addition, IL-33 protein levels were positively correlated with IFN-gamma mRNA levels in all groups except cervical cancer (CA) group (r = 0.546, P < 0.01). In vitro, IFN-gamma was also found to upregulate IL-33 expression in human epidermal keratinocytes (NHEKs) in a dose-dependent manner. However, CA tissues did not show further reduced IL-33 protein and mRNA levels compared with severe CIN tissues (P > 0.05). IFN-gamma mRNA levels were even higher in CA tissues than in severe CIN tissues (P < 0.05). Therefore, in cervical precancerous tissues, IL-33 levels were lower in more severe lesions and that may be related to diminished local IFN-gamma.