A shift to a peripheral Th2-type cytokine pattern during the carcinogenesis of cervical cancer becomes manifest in CIN III lesions

Abstract

Background: A shifted balance between T helper 1 (Th1)-type and Th2-type cytokines has been hypothesised in cervical dysplasia Aims: To evaluate possible deregulation of the cytokine network by estimating the expression of peripheral cytokines in different stages of cervical disease and in relation to the presence or absence of high risk human papillomavirus (HR-HPV). Methods: Twenty one HR-HPV positive women with high grade cervical intraepithelial neoplasia (CIN II-III) and 12 patients with invasive cervical carcinoma formed the study groups. Two control groups consisted of 10 HR-HPV positive and 11 HR-HPV negative women without CIN. Differences in leucocyte subgroups were evaluated by a differential leucocyte count. Plasma concentrations of tumour necrosis factor a (TNFa), TNFa receptors TNFRI and TNFRII, interferon c (IFNc), interleukin 2 (IL-2), IL-12, IL-4, and IL-10 were determined by enzyme linked immunosorbent assays. Results: Leucocyte counts in patients with CIN III and carcinoma were significantly higher than in controls. Plasma IFNc concentrations were significantly lower in patients with CIN III and carcinoma than in women with CIN II or controls. Plasma concentrations of IL-12, IL-2, IL-4, and TNFa did not differ significantly between groups, but significantly lower plasma concentrations of TNFRII were found in CIN III and carcinoma compared with CIN II. IL-10 was detected with increased frequency in the plasma of patients with CIN III and carcinoma. Conclusions: These results indicate that a shift to a Th2-type cytokine pattern during the carcinogenesis of cervical cancer occurs in women with CIN III lesions.

Concentration levels of IL-10 and TNFαcytokines in patients with human papilloma virus (HPV) DNA+and DNA−cervical lesions

“…On the other hand, higher levels of IL-10 were generally observed in the secretions of HPV DNA + patients with progressive cervical lesions (i.e., HSIL and cervical cancer stages) than in those with less severe lesions (i.e., ASCUS and LSIL stages); this was also the same trend among the DNA − patients. This is somewhat in line with the findings of Bais et al (2005), who demonstrated that serum IL-10 levels increased significantly as staging changed from dysplasia to invasive carcinoma, while levels of TNFα showed no significant modifications between stages. IL-10/TNFα in patients with HPV DNA + and DNA − cervical lesions 171…”

Effect of human papillomavirus infection on the immune system and its role in the course of cervical cancer

“…Distorted equilibrium between type 1 T-helper cells (Th1) and Th2 cell is another property of cellular immunity during hrHPV infection (34). There is a marked Th2 cytokine profile in intraepithelial and invasive cervical lesions.…”

Cytokines and Markers of Immune Response to HPV Infection

“…Abike et al (Abike, Engin et al 2011) measured neopterin, often considered a marker of immune activation, and found lower concentrations in HPV-positive versus HPV-negative women with normal through high-grade histology. Unlike the earlier studies, Bais et al (Bais 2005) measured numerous cytokines simultaneously (IL-2, IL-4, IL-10, IL-12, IFN-, TNF-), as well as soluble markers (sTNFRI and sTNFRII) in plasma. They discovered that higher mean IL-2 levels alone were associated with carcinogenic HPV positivity.…”