Cytokines of Cervical Mucosa and Human Papilloma Virus Infection of the Cervix: A Descriptive Study

Abstract

Objective: The production of cytokines by various cervical cells can be triggered by antigenic stimuli, including human papilloma virus (HPV) infection. The aim of the present study was to evaluate differences in cytokine levels between various intraepithelial cervical lesions. Study Design: A total of 97 women participated in this descriptive study. Within our study population, 27 subjects presented with high-grade squamous intraepithelial lesions (HSIL), 48 with low-grade squamous intraepithelial lesion (LSIL) and 22 with a normal smear. Colposcopy and directed biopsy were performed as needed. To confirm the presence of HPV, an HPV-DNA test was performed using polymerase chain reaction. Using flow cytometry to ThinPrep cervical samples, we assessed the family of interleukins (ILs), including IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor (TNF)-α and TNF-β and transforming growth factor-β₁. Statistical analyses were performed using the Statistical Package for the Social Sciences (SPSS for Windows; version 20.0). Results: Significantly lower levels of IL-1α, IL-2, IL-4 and TNF-α were detected in cervical samples obtained from the LSIL group when compared to samples obtained from the HSIL group. Conclusion: Significant differences in tissue cytokine levels exist between intraepithelial cervical lesions obtained from patients presenting with HSIL versus LSIL.

Interleukin IL-1α, IL-6, IL-8, IL-10 Expression in Different Staging of Cervical Intraepithelial Neoplasia

“…Our data indicates that there is a shift in local cytokine expression in both the epithelium and stroma in different CIN staging. According to literature resources, and as proven by our study, the IL-1α expression tends to increase from CIN II to CIN III (7,18). However, some researchers say that HPV induces downregulation of IL-1 expression in mRNA and protein level (25), thus a decrease in IL-1α expression is expected, however this was not seen in our study as IL-1α expression increased from CIN II to CIN III, indicating that IL-1α is probably not as important and as predictable.…”

“…It also stimulates leukocyte adherence to the endothelium by upregulation of ICAM-1, VCAM-1 and E-selectin (16). According to different research data, the expression of IL-1α is higher in CIN compared to healthy cervix uteri tissue (7,23,30), and it is even higher in CIN III compared to CIN I (18,30). It has an ability to induce normal and tumour cell growth (4,7,12,37).…”

Downregulation of IL-2 and IL-23 in Cervical Biopsies of Cervical Intraepithelial Lesions: A Cross-Sectional Study

“…We measured cervical levels of IL-2 and IL-4 to assess the Th2 response required for lymphocyte activation, differentiation, and proliferation [21]. Some studies have reported elevated levels of IL-2 and IL-4 in women with cervical intraepithelial neoplasia and high-risk HPV infection [9,16,31]; the predominance of Th2-type responses may lead to a weak cellular immune response to HPV and thus predispose to the development of highgrade cervical lesions and cervical cancer [19,20,32]. In contrast, we found that IL-2 levels were significantly decreased in HSIL and LSIL samples compared to NSIL samples.…”

“…Thus, IL-10's immunosuppressive and pleiotropic effects could favor an immunosuppressive microenvironment in the cervix, facilitating lesion progression [51]. Indeed, various studies have demonstrated an association between elevated IL-10 levels and cervical intraepithelial lesions, cervical cancer, and persistent HPV infection [9,10,52], and it has been suggested that IL-10 overexpression may play a critical role in creating an immunosuppressive microenvironment that favors progressive cervical disease and immune evasion by HPV [53]. In contrast, other studies suggest that low IL-10 levels might facilitate development of various types of cancers, including cervical cancer [54], and that higher levels of IL-10 may be associated with clearance of HPV infection [55].…”

“…Most studies on local immune response to HPV collect cervical mucus for cytokine measurements using either an endocervical brush or a cervicovaginal lavage [8][9][10][11][12][13][14][15][16], which essentially measures the spillover from cells located at the surface epithelium into the luminal fluid [17]. However, cells in other locations also release many cytokines involved in the immune response to infection.…”