Analysis of interleukin 6 gene expression in cervical neoplasia using a quantitative polymerase chain reaction assay: evidence for enhanced interleukin 6 gene expression in invasive carcinoma.

Interleukin 6 (IL-6) is a multifunctional cytokine which has recently been shown to act in vitro as a growth factor for cervical carcinoma cell lines. This prompted us to measure IL-6 gene expression using a new quantitative polymerase chain reaction assay in 13 invasive cervical cancers, 5 cases of cervical intraepithelial neoplasia, and 2 normal cervix. A significant increase in the expression of the IL-6 gene in invasive cervical carcinoma as compared to cervical intraepithelial neoplasia and normal cervix was demonstrated (P < 0.05). Unlike IL-6, the expression of other cytokine genes such as gamma-interferon was not correlated with any particular cervical histological lesion. Immunohistochemical analysis identified IL-6 protein only on stroma cells which, based on morphological criteria, most likely belong to the macrophage lineage. This was reinforced by the correlation observed between IL-6 gene expression and macrophage tumor infiltration (P < 0.007). No IL-6 immunostaining of cervical tumor cells was shown. Therefore this study confirms, in vivo, that IL-6 may play a role in the pathogenesis of carcinoma of the uterine cervix since its increased expression is associated with advanced neoplastic cervical lesions. In contrast to in vitro studies, the stromal origin of IL-6 suggests that this cytokine may modulate tumor cell proliferation by a paracrine rather than an autocrine mechanism.