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Mediators of Inflammation
Volume 2007, Article ID 24147, 8 pages
Research Article

Cytokine Release in HR-HPV(+) Women without and with Cervical Dysplasia (CIN II and III) or Carcinoma, Compared with HR-HPV() Controls

1Department of Obstetrics and Gynaecology, Erasmus University Medical Center, CA, Rotterdam 3000, The Netherlands
2Department of Pathology, Erasmus University Medical Center, CA, Rotterdam 3000, The Netherlands
3Department of Public Health, Erasmus University Medical Center, CA, Rotterdam 3000, The Netherlands
4Department of Pathology, Vrije Universiteit Medical Center, Amsterdam MB 1007, The Netherlands

Received 1 October 2007; Accepted 16 October 2007

Copyright © 2007 Aagje G. Bais et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Aims. 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 α (TNFα), interferon γ (IFNγ), 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 IFNγ 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.