Cytokine profile in cervical mucosa of Japanese patients with cervical intraepithelial neoplasia

Takashi Iwata, Takuma Fujii, Kenji Morii, Miyuki Saito, Juri Sugiyama, Hiroshi Nishio, Toru Morisada, Kyoko Tanaka, Tomonori Yaguchi, Yutaka Kawakami, Daisuke Aoki

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Background: Immune responses in the uterine cervix are considered to play an important role in persistent human papillomavirus (HPV) infection and carcinogenesis, but many aspects of the mechanism are still unclear. The goal of this study was to measure cytokines to analyze immune responses in patients with cervical intraepithelial neoplasia (CIN). Materials and methods: The levels of 17 cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, INF-γ, MCP-1, MIP-1β, and TNFα) in cervical mucus were simultaneously measured using a multiplex immunoassay in 52 high-grade squamous intraepithelial lesion (HSIL) cases and overproduction of IL-1β, IL-8, and MIP-1β was identified. The levels of these 3 cytokines were measured in 130 patients with or without CIN lesions using enzyme-linked immunosorbent assay. The associations of the cytokine levels with the cytology, infecting HPV type, and status of cigarette smoking were investigated Results: IL-1β and IL-8 levels were associated with the cytology, and these levels were higher in HSIL cases than in NILM (negative for intraepithelial lesion and malignancy) and LSIL (low-grade squamous intraepithelial lesion) cases (P = 0.005, P = 0.001, respectively). The MIP-1β level was significantly lower in smokers (P = 0.018) and high-risk (HR)-HPV-infected patients (P = 0.021). Conclusions: Enhanced expression of IL-1β and IL-8 indicates that Th2 inflammatory responses become stronger in the local uterine cervical region with the progression of CIN lesions, and a decrease in the MIP-1β level may be advantageous for immunoescape of HPV. Cigarette smoking may further facilitate persistent HPV infection.

Original languageEnglish
Pages (from-to)126-133
Number of pages8
JournalInternational Journal of Clinical Oncology
Issue number1
Publication statusPublished - 2015 Feb


  • CIN
  • Cigarette smoking
  • Cytokine
  • Cytology
  • HPV

ASJC Scopus subject areas

  • Surgery
  • Hematology
  • Oncology


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