Inverse modulation of IL-10 and IL-12 in the blood of women with preneoplastic lesions of the uterine cervix

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Abstract
It has been postulated that an impaired immune response may contribute to the progression of human papillomavirus (HPV)-associated preneoplastic lesions. Based on this hypothesis, we evaluated the cytokine production in the blood of patients with squamous intraepithelial lesions (SIL) of the uterine cervix. The levels of type-1 (interferon-gamma (IFN-γ) and IL-12) and type-2 (IL-4 and IL-10) cytokines were measured in whole blood culture supernatants of patients with low- and high-grade SIL and control women. There was no difference in IL-4 and IFN-γ levels between patients with SIL and the control group. In contrast, the ratio of IL-12/IL-10 levels was significantly lower in patients with SIL compared with the control group. A lower IL-12/IL-10 ratio in women with SIL was also observed when peripheral blood mononuclear cell (PBMC) culture supernatants and plasma samples were analysed. In patients, neither the lower expression of the CD3ε chain nor the higher frequency of HLA-DRB1*1501 expression could be correlated with abnormal cytokine production. These results suggest that a part of the cytokine network, namely IL-10 and IL-12, is perturbed in patients with SIL. A better knowledge of the role of these cytokines in regulating the growth of HPV-associated SIL might have practical implications for the development of vaccines or immunomodulatory strategies in the treatment of cervical cancers.