Cytokine Expression in the Cervical Stroma of HIV-Positive and HIV-Negative Women with Cervical Intraepithelial Neoplasia

Abstract

Cervical intraepithelial neoplasias (CINs) are a major public health issue. The prevalence of CINs is higher in women with the human immunodeficiency virus (HIV). The objective of this study was to determine whether there are differences in the immune responses in the cervical stroma of HIV-infected and -uninfected women with CIN. The responses were assessed according to the immunohistochemical expression of cytokines interleukin (IL)-4, IL-12, interferon gamma (IFN-γ), and tumor growth factor beta (TGF-β). In addition, we determined whether there were differences in the local immune responses between patients with CIN1 and CIN 2/3. A cross-sectional study was performed using material collected by cervical conization in HIV-infected and -uninfected women with CIN. The conization was performed using loop electrical excision procedure (LEEP) from January 1999 to May 2004. The evaluation of cytokines in the cervical stroma was based on immunohistochemistry. No differences were found between the two groups of women regarding HIV status. However, the associations between IL-12 expression and CIN 2/3 (p=0.016) in HIV-infected women and between IL-4 expression and CIN 1 (p=0.0456) in HIV-infected women were significant when the interaction between HIV infection and lesion grade was assessed. Additionally, a significant association between TGF-β expression and CIN 2/3 in both groups was observed regardless of HIV infection (p=0.000). An interaction between HIV infection and CIN grade was detected because IL-12 and IL-4 expression increased in the presence of HIV infection. Regarding the CIN grade, there was a high prevalence of TGF-β in CIN 2/3 lesions, which reflected the predominance of an immunoregulatory environment.