Investigation of cytokines in cervical mucus of different groups with cervical intraepithelial neoplasia
Authors:   Peoples' Friendship University of Russia named after Patrice Lumumba, Rieger A.N. ,   Moscow, Russian Federation, Antonova I.B. ,   Russian Scientific Center of Roentgenoradiology; Moscow, Russian Federation, Kharchenko N.V. ,   Peoples' Friendship University of Russia named after Patrice Lumumba; Moscow, Russian Federation, Kaprin A.D. ,   National Medical Research Radiological Center; Moscow, Russian Federation
Published: February 2024

Abstract Aim. Evaluation of cytokine profile in cervical mucus of patients with different degrees of cervical intraepithelial neoplasia (CIN). Design. One-central prospective open cohort incomed intervention study Materials and methods. Thirty female patients aged 18 to 49 years were included in the study. The control group (А) consisted of 10 HPV-negative patients without cervical pathology. Group B included 10 patients with low grade squamous cell intraepithelial lesion of the cervix (LSIL). Group C included 10 patients with high grade squamous cell intraepithelial lesion of the cervix (HSIL). Cervical mucus was collected from all the study participants to determine the levels of various cytokines. Cytokine content was determined using Bio-Plex Pro Human Cytokine 27-plex Assay Bio-Plex Pro™ commercial kit using Bio-Plex Pro™ commercial kit manufactured by Bio-Rad Laboratories, Inc. (USA) on a Luminex 200 analyzer (Luminex Corporation, USA). Statistical processing was performed using Excel 365 and SPSS 20.0 software package. Differences were recognized as statistically reliable (the null-hypothesis was rejected) at p < 0.05. Results. Evaluating the obtained data of the level of cytokines and growth factors in cervical mucus, numerous differences were found between the control group and patients with CIN of different severity. In group B compare to control group was observed statistically significant decrease from 2 to 100 times of the content of EOTAXIN, Interleukin-17α (IL-17α), IL-7, IL-8, IL-9, Interferon-gamma-induced protein 10 (IP-10), Monocyte chemoattractant protein 1 (MCP-1) and Platelet-derived growth factor (PDGF-BB). Between group C and control group were found statistically essential differences in the values of 21 out of 27 factors: granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-10, IL-12p70, IL-13, IL-15, IL-17α, IL-1ra, IL-1β, IL-2, IL-5, IL-6, PDGF-BB, Tumor necrosis factor alpha (TNF-α) and Vascular endothelial growth factor (VEGF) were elevated. In contrast, the concentrations of other cytokines: Fibroblast growth factor (FGF), Interferon-γ (IFN- γ), IL-7, IL-8, IL-9, IP-10 and MCP-1 in cervical mucus were significantly lower compared to controls. In addition to the described differences, similar changes in cytokine content were found in groups B and C. In both mild and severe cervical changes the concentration of IL-7, IL-8, IL-9, IP-10 and MCP-1 in the mucus was significantly lower than in the control group. At the same time, differences of the opposite nature were also observed. In particular, the level of IL-17α and PDGF-BB in the studied material in patients with severe CIN was significantly higher compared to the control group, and in case of mild changes — significantly lower. Conclusion. Thus, the concentration of cytokines in the cervical mucus of patients with CIN is significantly different from the local cytokine profile of healthy women. Further studies of cytokine involvement in the development of CIN will allow to characterize more precisely the mechanisms of carcinogenesis of the female reproductive system. Key words: cervical intraepithelial neoplasia, cytokine profile, immune response, immunosuppressive cytokines, keratinocytes.