Cytokine expression in squamous intraepithelial lesions of the uterine cervix: implications for the generation of local immunosuppression
We have addressed the notion that the progression of cancer of the uterine cervix is associated with a preferential constraint on the development of a type 1 cellular mediated response, which is necessary to efficiently eliminate (pre)neoplastic cells. Based on the importance of cytokines in the regulation of an appropriate immune response, we have evaluated the expression of IL‐12p40, IL‐10 and transforming growth factor‐beta 1 (TGF‐β1). Using reverse transcriptase‐polymerase chain reaction (RT‐PCR), the expression of these three cytokines was evaluated in both low‐grade (LG) and high‐grade (HG) cervical squamous intraepithelial lesions (SIL) and in normal exocervix and transformation zone biopsies. Our results show that the average level of IL‐12 increases within both the LG and HG SIL, compared with both control groups. Interestingly, the percentage of HG SIL expressing IL‐12p40 was lower compared with LG SIL. In contrast, the expression of IL‐10 increased in parallel with the severity of the lesion to a maximal level in HG SIL. Using immunohistochemistry, we ascertained the presence of IL‐12 protein in SIL and IL‐10 protein in the transformation zone and SIL biopsies. Both IL‐12‐ and IL‐10‐producing cells were localized in the stroma, not within the SIL. Furthermore, in this study we also observed that the region of the cervix the most sensitive to lesion development, the transformation zone, was associated with higher average levels of the immunosuppressive cytokines IL‐10 and TGF‐β1.