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Cytokine Growth Factor Rev. 2017 Apr;34:1-13. doi: 10.1016/j.cytogfr.2017.03.002. Epub 2017 Mar 23.

The role of interleukin 10 in human papilloma virus infection and progression to cervical carcinoma.

Author information

1
Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, State University of Londrina, 86.057-970, Paraná, Brazil. Electronic address: nandabrandao@hotmail.com.
2
Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, State University of Londrina, 86.057-970, Paraná, Brazil. Electronic address: anapaulalombardi91@gmail.com.
3
Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, State University of Londrina, 86.057-970, Paraná, Brazil. Electronic address: guilherme_cebinelli@hotmail.com.
4
Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, State University of Londrina, 86.057-970, Paraná, Brazil. Electronic address: klebertrugilo@hotmail.com.
5
Laboratory of Molecular Genetics and Immunology, Department of Pathological Sciences, State University of Londrina, 86.057-970, Paraná, Brazil. Electronic address: karen.brajao@gmail.com.

Abstract

Although Human Papillomavirus (HPV) exerts a vital influence on cervical carcinogenesis, other factors influence the development of a squamous intraepithelial lesion (SIL) that may or not progress to cervical cancer. Among several cytokines, Interleukin 10 (IL-10) stands out as an important anti-inflammatory factor, leading to immune system evasion through an immunosuppressive state. In the cervical microenvironment, during different stages of HPV infection, IL-10 production can be induced and maintained by different cell sources, including infected keratinocytes, some subsets of dendritic cells (DC), tumor associated macrophages (TAM), T regulatory cells (Treg) and tumor cells. Further, a wide range of effects can be exerted by IL-10 on different cell populations, such as inhibiting proinflammatory cytokine production, DCs differentiation, antigen presenting function and T-helper 1 (Th1) polarization. IL-10 is one of several cytokines involved in cancer development and sustenance, although its role in cancer is still controversial and poorly understood. However, cervical IL-10 levels tend to increase in parallel to SIL development and are even higher within cervical tumors. Accumulating data have shown that after HPV infection, IL-10 levels are enhanced as a result of HPV E2, E6 and E7 proteins action over IL-10 gene transcription, while IL-10 stimulates HPV E6 and E7 expression. Therefore, this interplay between HPV and IL-10 creates a vicious cycle that could favor an immunosuppressive microenvironment in the cervix, facilitating the progression of a simple HPV infection to SIL or cervical cancer.

KEYWORDS:

Cervical carcinoma; Human papillomavirus; Immune modulation; Interleukin 10; Squamous intraepithelial lesions

PMID:
28365229
DOI:
10.1016/j.cytogfr.2017.03.002
[Indexed for MEDLINE]

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