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

Abstract

Summary Introduction. Cervical cancer is the fourth most common form of cancer in women [19]. The precancerous stages are divided into three distinctive stages, labelled cervical intraepithelial neoplasia (CIN) I, II and III. One of the aetiological factors is chronic inflammation in cervical tissue, most often induced by Human papilloma virus (HPV). 88,5% of the patients regress from low grade intraepithelial changes to unchanged epithelium [14]. It has been proposed that cytokine balance plays a key role in the development of high grade epithelial changes (CIN I – CIN III) in the remaining 11.5% of patients, however, the exact trigger of this event remains to be found. Aim of the Study. The aim of the study was to determine three pro-inflammatory (IL-1α, IL-6, IL-8) and one anti-inflammatory (IL-10) interleukin expression in different CIN cervix uteri biopsies. Material and methods. 16 biopsies were obtained with different CIN staging: one with CIN I stage, five with CIN II stage and 10 with CIN III stage. The samples were stained with haematoxylin and eosin and immunohistochemistry for IL-1α, IL-6, IL-8 and IL-10. Slides were evaluated semi-quantitatively grading the intensity of positively stained structures in the visual field. Results. Examination of the samples yielded the following: IL-1α expression increased from CIN II to CIN III in squamous epithelium, while IL-8 expression decreased. A few IL-1α containing inflammatory cells were found in all CIN stages. IL-8 expression in subepithelium and the number of inflammatory cells decreased from CIN II stage to CIN III, although, it increased in the blood vessel endothelium. Conclusions. There was constant moderate expression of both IL-6 and IL-10 during all CIN stages, except for inflammatory cells, where IL-6 expression was high during all stages, yet there were few IL-10 containing cells during CIN. The balanced expression of both cytokines suggests that pro- and anti-inflammatory cytokine balance has an important role in CIN morfopathogenesis. The high expression of IL-6 in inflammatory cells and constant expression trough CIN staging indicates sustentation of chronic inflammation and production of other cytokines, such as IL-8, IL-1α. The variable IL-8 expression and its decrease in CIN III stage suggests the depletion of IL-8 production. The high expression of cytokines in blood vessel endothelium indicates their important role in CIN morfopathogenesis.

Cervical Microbiota Influences Cytokine Diversity in Cervical Intraepithelial Neoplasia among Rural Women in the Akyemansa District of Ghana

“…As anti-inflammatory cytokines, IFN-γ and TNF-α are immunostimulatory and have antitumour properties [12,13]. IL-6 cytokine in CIN, then, acts as inflammatory via the transsignalling pathway to be antiapoptotic and also increases the expression of vascular endothelial growth factor (VEGF) via the STAT3 pathway to promote cancerogenesis [14][15][16]. IL-4 and IL-10, on the other hand, are immunoinhibitory cytokines which promote tumour growth [10,12].…”