STATE OF CYTOKINE PROFILE IN PATIENTS WITH ADENOMYOSIS

Abstract

Introduction. Adenomyosis is an important problem of modern gynecology, which causes significant fertility declines, leads to disability, dysfunction of adjacent organs, decreased quality of life of women. Objective: to study the state of cytokine profile in patients with adenomyosis.Material and methods. 35 female patients of whom 20 (57.1 %) with adenomyosis of I degree (study group) and 15 (42.9%) healthy female patients (control group) were examined. We determined the content of cathelicidin (LL-37) and β-defensin IL-1β, 4, 6, 10, 18, TFN-α, VEGF in blood serum, cervical mucus and uterine lavage by immunoenzyme method. To assess cytokine imbalance, we used a ratio between IL-1β/IL-10, IL-6/IL-10, TFN-α/IL-10, IL-4/ IFN-γ. Local immunity was studied in women depending on the presence of genital pathogens. In cervical mucus, we determined the presence of HSV-1.2, CMV by the PCR method. In peripheral blood - the presence of HSV-1.2, CMV specific IgM, IgG.Results. Determination of DNA of HSV1.2, CMV pathogens by PCR analysis of cervical mucus of patients with adenomyosis showed the presence of mono-viral contamination of HSV1.2 and CMV in 40 % of cases. Moreover, HSV1.2 was detected 1.7 times more frequently than CMV (p<0.05). The proportion of mixt-viral contamination (HSV1.2+CMV) was 20 %.Six (30 %) patients with adenomyosis had an increased IgG titer against HSV1,2, five (25 %) had an increased IgG titer against CMV. No IgM against HSV1.2, CMV was detected. The study of cytokine profile in blood serum of patients with adenomyosis revealed a statistically significant increase in the level of pro-and anti-inflammatory cytokines. The increase in proinflammatory cytokines was less significant, and the concentration of anti-inflammatory cytokines was more significant, especially IL-10, indicating a cytokine imbalance with Th2-type cytokines predominating. In addition, in women with adenomyosis, an increase in the concentration of pro-and anti-inflammatory cytokines was observed in cervical mucus and uterine lavage, and the dynamics correlated with the values in blood serum; the degree of increase exceeded the values in blood serum. An increase of angiogenesis factor (VEGF) both in blood serum and locally may contribute to activation of vascular growth and ectopic endometrium. On the one hand, antimicrobial peptides decrease in blood serum and to a greater extent locally (defensin in cervical mucus: 384.5±39.1 pg/ml, in uterine lavage 252.2±24.8 pg/ml; in the control group – 447.1±45.3 pg/ml, 446.2±39.3 pg/ml, respectively; ±6.8 pg/ml, in the control group – 62.2±6.1 pg/ml. In all probability, these immune changes through the mechanism of epithelial-mesenchymal transition stimulate the migration of endometrial cells to the myometrium; endocrine imbalance may also contribute to this.Conclusions. The results of the studies showed a pronounced imbalance of the cytokine profile in patients with adenomyosis in case of genital infection. Immune disorders formed against the background of viral pathogens can contribute to the penetration of the endometrium into the myometrium and the development of the disease. The subject for further research should be the search for adequate therapeutic approaches aimed at the regulation of increased proliferation and invasion of the endometrium.