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

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Abstract

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.

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Acknowledgments

This work was supported by a grant from the Smoking Research Foundation of Japan. The authors also received a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sport and Technology, Japan (23592462).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan

    Takashi Iwata, Takuma Fujii, Miyuki Saito, Juri Sugiyama, Hiroshi Nishio, Tohru Morisada, Kyoko Tanaka & Daisuke Aoki

  2. Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan

    Takuma Fujii

  3. Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan

    Kenji Morii, Tomonori Yaguchi & Yutaka Kawakami

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  1. Takashi Iwata
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  2. Takuma Fujii
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Correspondence to Takashi Iwata.

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Iwata, T., Fujii, T., Morii, K. et al. Cytokine profile in cervical mucosa of Japanese patients with cervical intraepithelial neoplasia. Int J Clin Oncol 20, 126–133 (2015). https://doi.org/10.1007/s10147-014-0680-8

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  • DOI: https://doi.org/10.1007/s10147-014-0680-8

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