Cytokine expression profiles in cervical mucus from patients with cervical cancer and its precursor lesions. (August 2019)

• Record Type: Journal Article
• Authors: Otani, Sayaka; Fujii, Takuma; Kukimoto, Iwao; Yamamoto, Naoki; Tsukamoto, Tetsuya; Ichikawa, Ryoko; Nishio, Eiji; Iwata, Aya
• Is Part Of: Cytokine. Volume 120(2019)
• Page Start: 210
• Page End: 219
• Publication Date: 2019-08
• Subjects: Chemokine -- Immune response -- Cervix -- Papillomavirus; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2019.05.011
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: Cytokine expression in cervical mucus was significantly increased with disease severity. In mucus from HPV-positive patients, some sets of cytokines were co-expressed. GM-CSF and RANTES are important immunoregulatory cytokines in cervical neoplasia. Abstract: Human papillomavirus (HPV) infection can persist in the cervical epithelium without provoking a strong host immune response, leading to the development of cervical cancer. Cytokines, which mediate innate and adaptive immune activities, are secreted in the cervical mucus; however, there is currently no appropriate method for assessing cytokine levels in mucus specimens. Here, we employed multiplexed bead-based immunoassays to examine cytokine levels in cervical mucus using both weighted-volume and total protein concentration methods to adjust for different specimen volumes in individual patients. Out of 18 cytokines initially examined in the primary cohort patient group ( n = 28), 14 were detected in more than 10% of the samples. Of these 14 cytokines, expression levels of interferon (IFN)-γ, granulocyte–macrophage colony-stimulating factor (GM-CSF), RANTES, and eotaxin were significantly increased with the disease severity in the secondary cohort patient group ( n = 235). We also examined associations between cytokine levels and clinical parameters, such as cytology and HPV genotype. Of the 14 cytokines, granulocyte colony-stimulating factor (G-CSF) was downregulated in HPV-positive specimens. Examination of co-expression patterns of cytokines in relation to HPV infection status revealed that several pairs of cytokines were simultaneously upregulated in HPV-positive cases, including INF-γ and interleukin (IL)-17A, GM-CSF and monocyte chemoattractant protein-1 (MCP-1), GM-CSF and RANTES, IL-17A and RANTES, and MCP-1 and eotaxin. Interestingly, upregulation of GM-CSF and RANTES might reflect a shift in immuno-regulatory cytokines in HPV-positive specimens, potentially associated with more severe cervical neoplasia.