title: Cytokine profile in cervical mucosa of Japanese patients with cervical intraepithelial neoplasia.
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).
  
  
  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.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan, iwatatakashi@1995.jukuin.keio.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.forename: Takuma
authors.initials: T
authors.lastname: Fujii
authors.forename: Kenji
authors.initials: K
authors.lastname: Morii
authors.forename: Miyuki
authors.initials: M
authors.lastname: Saito
authors.forename: Juri
authors.initials: J
authors.lastname: Sugiyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishio
authors.forename: Tohru
authors.initials: T
authors.lastname: Morisada
authors.forename: Kyoko
authors.initials: K
authors.lastname: Tanaka
authors.forename: Tomonori
authors.initials: T
authors.lastname: Yaguchi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
mesh_terms: D000328:Adult; D044466:Asian People; D054407:Chemokine CCL4 / Q000276:immunology; D018450:Disease Progression; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D016209:Interleukin-8 / Q000276:immunology; D009092:Mucous Membrane / Q000276:immunology* / Q000473:pathology; D030361:Papillomavirus Infections / Q000276:immunology / Q000473:pathology; D012907:Smoking / Q000276:immunology; D065310:Squamous Intraepithelial Lesions of the Cervix / Q000276:immunology / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000276:immunology* / Q000473:pathology
chemical_list: D054407:Chemokine CCL4; D053583:Interleukin-1beta; D016209:Interleukin-8