Pegylated-interferon-alpha treatment modifying T cell cytokine profile in tumor microenvironment of patients with cervical intraepithelial neoplasia

Objective: The goal of the investigation was to compare the profiles the cytokines IL-2, IL-12, IFN-$\gamma$, TNF-$\alpha$ , TGF-$\beta$, IL-4, IL-6 in the endocervical and serum secretions of patients with cervical intraepithelial neoplasia (CIN) who had good or poor response to immunotherapy with pegylated (PEG)-Interferon-alpha. Methods: The study was performed with 16 patients who had been diagnosed with CIN II and III. Each patient was submitted to six injections of PEG-Interferon-$\alpha$ -2b subcutaneously. After each injection, endocervical secretion and serum samples were collected for cytokine levels by ELISA. Results: Of the 16 women, 43.75% (n = 7) showed good clinical response and lesion regression after treatment as seen by histopathological analysis. When we analyzed the pre-therapy, locally we observed a higher concentration of IL-4 in patients who did not respond to treatment (P = 0.0229). After treatment, there was a significant reduction in IL-4 in unresponsive patients (P = 0.0304). Patients responsive to IFN-$\alpha$ had a reduction in the concentrations the TNF-$\alpha$ after treatment (P = 0.0313). Conclusion: Immunotherapy with PEG-Interferon-$\alpha$ can reduce the damage caused by HPV by decreasing local inflammation by reducing the cytokines IL-4 and TNF-alpha during treatment in endocervical secretion. It seems that the regression is related to the immunological profile, mainly local, before treatment, as in the case of IL-4 and TNF-alpha, promoting a Th2 profile in those patients with therapeutic failure.

Cytokines; Immunotherapy; Cervical intraepithelial neoplasia

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