In this study we measured serum concentrations of proinflammatory interleukin-6, interleukin-8, and interleukin-18 as well as anti-inflammatory interleukin-10 in 30 pregnant women with normal glucose tolerance, in 32 women with abnormal results of a 50-g glucose challenge test, and in 57 patients with gestational diabetes mellitus. Patients with gestational diabetes had significantly higher IL-6 (median 1.0 [0.7–1.5] vs. 0.7 [0.4–0.8] pg/ml, p=0.001), IL-8 (2.1 [1.1–4.2] pg/ml vs. 0.7 [0.4–0.9] pg/ml, p<0.0001), and IL-18 (249.3 [188.5–318.7] pg/ml vs. 186.7 [139.9–243.9] pg/ml, p=0.005) as well as lower IL-10 levels than healthy pregnant women (0.6 [0.5–1.5] pg/ml vs. 2.9 [1.8–3.2] pg/ml, p<0.0001). After adjusting for glucose, insulin, and BMI values, the differences in IL-8 and IL-18 became insignificant, whereas the differences in IL-6 and IL-10 levels remained highly significant (p<0.0001). The subjects with abnormal glucose challenge test results had higher IL-6 levels (0.9 [0.7–1.3] pg/ml, p=0.005) and similar levels of other cytokines as compared with the women with normal glucose tolerance. Our results suggest an impaired balance between circulating pro- and anti-inflammatory cytokines in patients with gestational diabetes; however, a significant contribution of maternal obesity to the increased levels of IL-8 and IL-18 should be underlined.

The eutopic endometrium of women with endometriosis, compared with disease-free individuals, contains certain molecular alterations, including the differential expression of microRNA (miRNA). The aim of the study was to compare the expression of the most relevant miRNAs in the eutopic endometrium of women with and without ovarian endometriosis.

Ovarian cancers pose the greatest challenge for gynecological oncology. They are a heterogeneous, rapidly progressing and highly lethal group of malignancies and their etiology is still poorly understood. Among many hypotheses, explaining the pathogenesis of malignant tumors, chronic inflammation seems to play a significant role, which was proved in cervical, hepatic and esophageal cancers. The processes of inflammation and carcinogenesis are very much alike. Their similarity was experimentally confirmed by epidemiological, immunological, biochemical and genetic studies. Additionally this view is supported by indirect epidemiological and clinical evidence linking ovarian cancer with pelvic inflammatory disease, endometriosis or polycystic ovary syndrome. Chronic inflammation is a key factor in the pathogenesis of these illnesses. Moreover ovulation involving repeated damage and repair of the ovarian surface epithelium is in fact an inflammatory process. In this review, we focus on the role of inflammation in cancer initiation, promotion and progression with special emphasis on the ovarian cancer. We discuss the potential involvement of the fallopian tubes, endometriosis and microenvironment of tumors represented by cytokines, chemokines, growth factors and various enzymes that destroy the extracellular matrix. Considering that molecular biology is currently rapidly evolving, we focus on the function of the mammalian target of rapamycin (mTOR) kinase and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) in the pathophysiology of inflammation and cancer.

BACKGROUND: Matrix metalloproteinases (MMPs) are a family of endopeptidases which play a role in the degradation and turnover of extracellular matrix proteins. Their action is regulated by specific tissue inhibitors called tissue inhibitors of metalloproteinases (TIMPs). METHODS: We measured the concentrations of total and active MMP-9 in peritoneal fluid of infertile women with mild or moderate endometriosis (n = 22) and compared them with those in a control group of infertile patients (n = 21). RESULTS: We found that the mean (±SD) total concentrations of MMP-9 in the peritoneal fluid of patients with endometriosis was 6.2 ± 1.8 ng/ml, in comparison with 2.9 ± 2.6 ng/ml in the control group (P = 0.001). Concentrations of active MMP-9 did not differ significantly between the groups. The concentrations of TIMP-1, after logarithmic transformation, were significantly lower (P = 0.017) in endometriotic peritoneal fluids than in peritoneal fluid of control women, 1.02 ± 0.21 ng/ml and 1.16 ± 0.18 ng/ml respectively. No correlation between stage of disease, steroid hormone concentration, MMP-9 (total and active) and TIMP-1 was found. CONCLUSIONS: These results suggest that a disturbed equilibrium exists between MMP-9 and TIMP-1 in peritoneal fluid of women with endometriosis. This may play an important role in the pathogenesis of the disease.

It is becoming increasingly evident that the eutopic endometrium of women with endometriosis shows certain genetic alterations which are not found in the endometrium of disease-free women. The aim of the study was to compare the expression level of mammalian target of rapamycin (mTOR) tumor suppressor and oncogene-related genes in the endometrium of women with and without endometriosis as well as in ovarian endometriosis. A total of 81 regularly menstruating patients were recruited in the study. We applied the micro fluidic gene array to examine the expression of 15 human tumor suppressor and oncogenes in eutopic endometrium of 40 women with endometriosis and 41 controls without endometriosis. In 14 patients with endometriosis, gene expression was also studied in matched ovarian lesions. We studied the following genes: NF1, RHEB, mTOR, PTEN, TSC1, TSC2, KRAS, S6K1, TP53, EIF4E, LKB1, PIK3CA, BECN1, 4EBP1 and AKT1. Immunohistochemical studies were subsequently performed for selected proteins. Of the 15 studied genes, we found significantly higher levels of oncogene AKT1 (P = 0.006) and tumor suppressor gene 4EBP1 (P = 0.01) mRNAs in the eutopic endometrium of women with endometriosis compared with control patients. Immunohistochemistry showed that 4EBP1 and AKT1 proteins were expressed in eutopic endometrium. Our results suggest that up-regulation of AKT1 and 4EBP1 in eutopic endometrium may be associated with the pathogenesis of endometriosis, but their precise role remains to be established.