title: Cytokine release in HR-HPV(+) women without and with cervical dysplasia (CIN II and III) or carcinoma, compared with HR-HPV(-) controls.
abstract: OBJECTIVE
  We investigated the effect of HR-HPV infection on the capacity of the cytokine network in whole blood cultures during carcinogenesis of cervical carcinoma.
  
  
  METHODS
  Thirty-nine women with moderate dysplasia, severe dysplasia, cervical carcinoma, or without dysplasia formed the study group. The control group consisted of 10 HR-HPV-negative women without CIN. Whole blood cultures were stimulated with phytohemagglutinin (PHA) and concentrations of tumour necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), interleukin 2 (IL-2), interleukin 12 (IL-12), interleukin 4 (IL-4), and interleukin 10 (IL-10) were determined by ELISAs.
  
  
  RESULTS
  A significant increase in cytokine release was detected in HR-HPV-positive women without dysplasia. In women with cervical cancer, release of IFNgamma and IL-12 was of the same magnitude as in HR-HPV-positive women without clinical manifestations. Most Th1-type/Th2-type ratios decreased form CIN II to CIN III, and increased from CIN III to invasive carcinoma.
  
  
  CONCLUSIONS
  (1) Infection with HR-HPV without expression of cervical dysplasia induces activation of the cytokine network. (2) Increases in ratios of Th1-type to Th2-type cytokines at the stage of cervical carcinoma were found by comparison with stage CIN III. (3) Significant changes in the kinetics of cytokine release to a Th2-type immune response in blood of women with cervical dysplasia occurred progressively from CIN II to CIN III.
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus University Medical Center, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Aagje G
authors.initials: AG
authors.lastname: Bais
authors.forename: Ilse
authors.initials: I
authors.lastname: Beckmann
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Ewing
authors.forename: Marinus J C
authors.initials: MJ
authors.lastname: Eijkemans
authors.forename: Chris J L M
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Peter J F
authors.initials: PJ
authors.lastname: Snijders
authors.forename: Theo J M
authors.initials: TJ
authors.lastname: Helmerhorst
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000378:metabolism / Q000821:virology*; D016022:Case-Control Studies; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008954:Models, Biological; D015233:Models, Statistical; D027383:Papillomaviridae / Q000378:metabolism*; D002578:Uterine Cervical Dysplasia / Q000378:metabolism / Q000821:virology*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000821:virology*
chemical_list: D016207:Cytokines