Monocyte chemotactic protein-1 concentration in peritoneal fluid of women with endometriosis and its modulation of expression in mesothelial cells

Objective: To investigate monocyte chemotactic protein-1 concentrations in the peritoneal fluid (PF) of women with or without endometriosis, then assess peritoneal mesothelial cells as a potential source of monocyte chemotactic protein-1.

Design: Prospective study.

Setting: University medical center.

Patient(s): Women with (n = 60) or without (n = 18) endometriosis.

Intervention(s): First monocyte chemotactic protein-1 levels in PF were measured, then mesothelial cells in culture were treated with cytokines.

Main Outcome Measure(s): In PF and culture supernatants, monocyte chemotactic protein-1 was measured by ELISA. In vitro monocyte chemotactic protein-1 messenger RNA expression was evaluated by Northern analysis.

Result(s): The median concentration of monocyte chemotactic protein-1 in PF of control women was 137 pg/mL (conversion factor to SI unit, 0.115; range, 12 to 418 pg/mL); that of women with moderate endometriosis was 205 pg/mL (range 65 to 6,000 pg/mL); and that of those with severe endometriosis was 1,165 pg/mL (0 to 2,602 pg/mL). Within the moderate to severe endometriosis group, monocyte chemotactic protein-1 levels were higher in women with untreated endometriosis (354 pg/mL range 0 to 6,000 pg/mL) than in women receiving GnRH agonist (128 pg/mL, range 0 to 216 pg/mL). In the control group, monocyte chemotactic protein-1 levels were higher in the proliferative phase than in the secretory phase. Mesothelial cells produced constitutively monocyte chemotactic protein-1; moreover, both interleukin-1 and tumor necrosis factor- induced higher levels of monocyte chemotactic protein-1.

Conclusion(s): Levels of monocyte chemotactic protein-1 in PF were higher during the proliferative phase than secretory phase of control women and increased in moderate to severe endometriosis. The regulated expression of monocyte chemotactic protein-1 may recruit macrophages into PF and contribute to the pathogenesis of endometriosis.     

Increased monocyte chemotactic protein-1 level and activity in the peripheral blood of women with endometriosis

OBJECTIVE: Our purpose was to evaluate monocyte chemotactic protein-1 in the peripheral blood of women with and without endometriosis. STUDY DESIGN: Fifty-seven patients with endometriosis at laparoscopy done for infertility and pelvic pain were compared with 44 fertile women with no evidence of endometriosis at tubal ligation by laparoscopy. Monocyte chemotactic protein-1 concentration in the plasma was determined by enzyme-linked immunosorbent assay and its biologic activity was evaluated by measuring monocyte chemotaxis with use of a human histiocytic cell line (U937). RESULTS: Monocyte chemotactic protein-1 concentrations (median and range of values) found in the plasma were higher in patients with endometriosis (163, 0 to 788 pg/ml) than in normal controls (0, 0 to 355 pg/ml). This elevation was significant only in the minimal stage of endometriosis (revised American Fertility Society stage I). However, increased chemotactic activity (mean number of migrating cells/mm² ± SEM) was found in the stages I (1240 ± 141), II (519 ± 30), and III-IV (523 ± 23) of the disease compared with normal controls (205 ± 20). A total of 35% to 44% of this activity was inhibited in the presence of an antibody specific to monocyte chemotactic protein-1. CONCLUSION: Endometriosis is associated with increased level and activity of monocyte chemotactic protein-1 in the peripheral blood. The elevation and activation of this cytokine could play a relevant role in the immunoinflammatory process associated with the disease. (Am J Obstet Gynecol 1996;175:1620-5.)     

Serum and peritoneal fluid immunological markers in adolescent girls with chronic pelvic pain

The aim of this study was to determine serum and peritoneal interleukin (IL)-2, IL-4, and monocyte chemotactic protein-1 levels as diagnostic markers of endometriosis in adolescent girls. The design of the study encompassed 50 adolescent girls, aged 13 to 19 years after menarche, with chronic pelvic pain who qualified for diagnostic laparoscopy. The patients were allocated into 2 groups: group I (endometriosis) consisted of subjects with diagnosed endometriosis (n = 33, 66%) and group II (control) whose laparoscopic examinations revealed no evidence of endometriosis (n = 17, 34%). IL-2, IL-4, and Monocyte chemotactic protein 1 concentrations in serum and peritoneal samples were assessed using commercially available human enzyme-linked immunosorbent assay kits. The results were analyzed statistically with the Statistica 8.0 computer software. The value of P < 0.05 was the level of statistical significance. The results in adolescents with endometriosis had significantly higher concentrations of serum IL-4 (3.90 ± 1.58 pg/mL vs. 3.04 ± 1.72 pg/mL; P = 0.04) and peritoneal fluid IL-4 (5.03 ± 8.92 pg/mL vs. 2.74 ± 1.11 pg/mL; P = 0.03), and lower peritoneal fluid IL-2 (92.44 ± 292.75 pg/mL vs. 174.23 ± 389.77 pg/mL; P = 0.01) compared with the control. In a receiver-operating characteristic analysis, serum IL-4 as well as peritoneal fluid IL-2 and IL-4 provided the best discriminative ability between subjects with endometriosis and controls. Using cutoff points for serum IL-4 (3.00 pg/mL), peritoneal fluid IL-2 (21.00 pg/mL) and IL-4 (2.7 pg/mL), relatively high odd ratios were obtained in the prediction of endometriosis in adolescents (3.2; 6.4; 3.3). The Serum IL-4, peritoneal IL-2 and IL-4 provided a good method of discrimination between subjects with endometriosis and controls.     

Maternal serum cytokines in labor, pregnancy and chorioamnionitis

The purpose of our study was to compare maternal serum levels of interleukin-6, interleukin-8, tumor necrosis factor-alpha and interferon-gamma in gravidities, during spontaneous term and preterm labor and their relation to histologic chorioamnionitis. METHODS: We investigated 61 women: 10 in preterm labor, 36 in term labor and 15 healthy pregnant nonlabouring controls. Venous bloods for cytokines determinations were obtained during the first stage of labor and during routine screening tests. Titers of cytokines were measured by means of ELISA technique. All births after preterm deliveries were examined to establish histologic chorioamnionitis. RESULTS: Serum levels of IL-6 and IL-8 were significantly elevated both in term (mean: IL-6: 17.5 +/- 58 pg/ml; IL-8: 148 +/- 215 pg/ml) and preterm labor (IL-6: 23 +/- 44 pg/ml; IL-8: 332 +/- 389 pg/ml) when compared to nonlabouring gravidities (IL-6: 5 +/- 7 pg/ml; IL-8: 14 +/- 11 pg/ml). IL-6 and IL-8 titers were statistically similar in term and preterm labors and in patients with and without histologic chorioamnionitis. TNF-alpha and IFN-gamma were not statistically analyzed because only a few patients had detectable serum levels of these cytokines. CONCLUSION: Serum levels of IL-6 and IL-8 in both: term and preterm labor are elevated in comparison to nonlabouring gravidities. The elevated levels of these cytokines are not connected with coexisting chorioamnionitis.     

Ethnicity and mode of delivery in 'low-risk' first-time mothers, East London, 1988-1997

OBJECTIVE: To test whether serum monocyte chemotactic protein-1 (MCP-1) chemokine levels correlate with endometriosis in infertile women. STUDY DESIGN: A group of women with endometriosis (n = 18, infertile) was compared with patients with uterine leiomyoma (n = 16, fertile), unexplained infertility (n = 5, infertile), and healthy women (n = 16, fertile). MCP-1 expression levels were evaluated by ELISA assay. The data obtained were statistically analyzed using the Mann-Whitney test. P-Values <0.05 were considered as significant. RESULTS: MCP-1 concentrations (median; range of values) in serum were as follows: women with endometriosis (221; 101-635 pg/ml), women with unexplained infertility (167, 114-234 pg/ml), women with uterine leiomyoma (137; 88-200 pg/ml), and healthy donors (123; 98-194 pg/ml). Significant differences were observed in the women with endometriosis compared with those with uterine leiomyoma (p = 0.02) and healthy donors (p = 0.002). Among the women with endometriosis, the level of significance in MCP-1 level at rAFS stages III-IV was higher than that at rAFS stages I-II compared with healthy donors and women with leiomyoma (p = 0.002 and p = 0.02, respectively). CONCLUSIONS: These data show that an increased level of MCP-1 can characterize infertile women with endometriosis. However, further studies are needed to be able to determine whether increased MCP-1 chemokine expression can be related to infertility or is a result of endometriosis progress.     

Cytokine profiles in serum and peritoneal fluid from infertile women with and without endometriosis

OBJECTIVE: To study the serum and peritoneal fluid cytokine profiles in infertile women with minimal/mild active endometriosis. METHODS: Fifty-seven consecutive infertile women undergoing laparoscopy for unexplained infertility had peritoneal fluid and serum samples obtained at the time of laparoscopy. The levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-1 beta (IL-1 beta), vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotatic protein-1 (MCP-1), RANTES, platelet derived growth factor (PDGF), soluble Fas (sFas), and soluble Fas Ligand (sFasL) in peritoneal fluid and serum were measured to compare the concentration in both biological fluids, in women who have minimal/mild red endometriosis using women with no endometriosis as controls. RESULTS: Peritoneal fluid levels of MCP-1, IL-8 and IL-6 were significantly higher in the endometriosis group (P < 0.012, P = 0.003, and P = 0.015, respectively). There was no significant difference in the peritoneal fluid levels of IL-1 beta, TNF-alpha, RANTES, VEGF, PDGF, sFas and sFasL in the two groups. Although serum levels of IL-8 were higher in women with endometriosis, the difference was not significant (P = 0.07). Serum levels of PDGF, IL-6, RANTES, IL-1 beta, TNF-alpha, and sFas, were not significantly different in the two groups. CONCLUSION: The elevated levels of MCP-1, IL-6, and IL-8 in peritoneal fluid but not serum may indicate the importance of local macrophage activating factors in the pathogenesis of endometriosis.     

离体异位子宫内膜细胞中单核细胞趋化蛋白-1的测定

目的　探讨异位子宫内膜细胞产生单核细胞趋化蛋白１（ＭＣＰ１）的临床意义。方法　收集１５ 例子宫内膜异位症患者的异位内膜组织进行体外细胞培养,分别加入纯培养液（ 对照组） 、含白细胞介素１β（ＩＬ１β）２ ｎｇ／ｍｌ（ＩＬ１β诱导组）及肿瘤坏死因子α（ＴＮＦα）２０ ｍｇ／ｍｌ（ＴＮＦα诱导组）的培养液培养４ 小时,应用斑点杂交、免疫组织化学及夹心酶联免疫吸附试验检测各组异位细胞中ＭＣＰ１ｍＲＮＡ蛋白的表达水平及其培养上清中ＭＣＰ１ 的含量。结果　与对照组相比,异位内膜细胞经ＩＬ１β及ＴＮＦα作用后表达的ＭＣＰ１ ｍＲＮＡ和蛋白水平显著增加（ Ｐ＜ ０．０１ ,Ｐ＜０．０５）;培养上清中ＭＣＰ１ 的含量也显著增加（Ｐ＜０ ．０１ ,Ｐ＜ ０．０５）。结论　ＩＬ１β及ＴＮＦα可刺激异位内膜细胞中ＭＣＰ１ 的表达显著增加,这可能和子宫内膜异位症的病变发展有关。     

Expression of inflammatory cytokines in serum and peritoneal fluid from patients with different stages of endometriosis

Objective: To investigate the level of inflammatory cytokines in endometriosis patients, and explore the relationship between IL-37 concentration and endometriosis stages.

Methods: Inflammatory cytokine concentrations from 27 patients with different stages of endometriosis and 52 controls without endometriosis were examined by ELISA. Then, the specificity and sensitivity of cytokines for distinguishing from controls and the different stages of endometriosis were analyzed using the ROC curve.

Results: The difference in serum concentrations of IL-37, IL-17A, IL-10, and IL-2 between the endometriosis and control groups was statistically significant (p?p?p?=?.0034), IL-10 concentrations in PF were significantly lower in the early-stages of endometriosis than in the more advanced groups (p?=?.0439), and IL-4 concentration in PF was significantly higher in more advanced endometriosis (p?=?.0228). The sensitivity and specificity of serum IL-37 for distinguishing endometriosis were 81.48% and 83.33%, respectively, and the cutoff concentration was 69.84?pg/ml. For IL-17A, the sensitivity and specificity were 96.30% and 100%, respectively, and the cutoff concentration was 57.54?pg/ml. For IL-10, the sensitivity and specificity was 92.59% and 100%, respectively, and the cutoff concentration was 3.301?pg/ml. For IL-2, the sensitivity and specificity were 74.07% and 93.75%, respectively, and the cutoff concentration was 1.813?pg/ml. For PF IL-2, the sensitivity and specificity were 29.73% and 100%, respectively, and the cutoff concentration was 1.06?pg/ml.

Conclusions: IL-37, IL-17A, IL-10, and IL-2 may play a significant role in immune response in endometriosis. IL-37 levels may be used as a diagnostic marker for endometriosis.     

The relationship between the levels of proinflammatory cytokines, and AFI value in pregnancies complicated by premature rupture of membranes

OBJECTIVE: The aim of the study was to test the relationship between maternal serum proinflammatory cytokines level and AFI (amniotic fluid index) in pregnancies complicated by premature rupture of membranes (PROM). MATERIALS AND METHODS: The maternal serum levels of IL-6, IL-1 beta and TNF-alfa were assessed in patients with PROM between 24-34 weeks of gestation (n = 45) by means of commercially available ELISA assays. The patients were divided in two groups according to AFI values: < 50 (n = 25) mm and < or = 50 mm (n = 20). Cytokine concentrations were compared between groups. RESULTS: The median concentrations of proinflammatory cytokines in maternal serum were: IL-6--5.74 pg/ml (range 3.24-3111 pg/ml), IL-1 beta--0.76 pg/ml (range 0.001-3.16 pg/ml), TNF-alfa--1332.46 pg/ml (range 2.13-1969.68 pg/ml). Compared to patients with AFI values > or = 50 mm, the group of patients with AFI < 50 mm had significantly higher concentration of IL-6 (6.61 pg/ml vs. 4.66 pg/ml; p = 0.002). No significant differences in IL-1 beta and TNF-alfa levels have been found between groups. The significant correlation have been observed between maternal serum level of IL-6 and AFI values (R = -0.47, p = 0.003), but not of IL-1 beta and TNF-alfa. CONCLUSION: The assessment of AFI values in pregnancies complicated by premature rupture of membranes seems to be the valuable method of early diagnosis in cases of intrauterine infection.     

Soluble interleukin-1 receptor type II blocks monocyte chemotactic protein-1 secretion by U937 cells in response to peripheral blood serum of women with endometriosis

OBJECTIVE: To assess the ability of peripheral blood serum from women with endometriosis to induce monocyte chemotactic protein-1 (MCP-1) secretion by monocytes and the putative role of the interleukin-1 (IL-1) system in endometriosis-associated monocyte activation. DESIGN: Cultures of U937 monocytic cells exposed to serum from normal women (control group) or women with endometriosis. SETTING: Gynecology clinic and human reproduction research laboratory. PATIENT(S): Seventy-nine women with endometriosis and 38 control women with no evidence of endometriosis at laparoscopy. INTERVENTION(S): Peripheral blood obtained a few days before laparoscopy. MAIN OUTCOME MEASURE(S): MCP-1 secretion in the culture medium and serum concentrations of soluble IL-1 receptor type II (sIL-1RII), IL-1beta, and IL-1alpha by ELISA or by enzyme immunometric assay. RESULT(S): Serum concentrations of sIL-1RII were significantly lower in women with stage I-II endometriosis than in control women, whereas serum concentrations of IL-1beta and IL-1alpha were comparable between the two groups. The serum of women with endometriosis induced higher secretion of MCP-1 by U937 cells than that of control women, particularly in the initial stages of endometriosis (stages I-II), and recombinant IL-1RII (rIL-1RII) significantly blocked that secretion. CONCLUSION(S): These findings point toward a deficiency in the mechanisms involved in the down-regulation of IL-1 actions at the systemic level and reveal sIL-1RII as a key factor involved in that process.     

Chemokines and human reproduction

Objective: To review the available information regarding chemotactic cytokines and their possible implications in human reproduction.

Design: A thorough literature and MEDLINE search was conducted to identify studies relating to the role of chemokines in ovulation, menstruation, implantation, cervical ripening and preterm labor, and endometriosis.

Result(s): Chemokines mediate leukocyte traffic through their specific receptors in various tissues. Although four families have been described to date, two remain the major subfamilies: -chemokines (with interleukin-8 as representative for this group), and β-chemokines (with monocyte chemotactic protein-1 as representative). Interleukin-8, monocyte chemotactic protein-1, and growth-regulated oncogene- are involved in follicular development and atresia, ovulation, steroidogenesis, and corpus luteum function. Interleukin-8 showed cycle-dependent expression in human endometrium, and at the same time, stimulated endometrial stromal cell growth, acting as an autocrine growth factor. Interleukin-8 has been identified in human amnion, chorion, decidua, and villous placenta, and its level increases during labor. Levels of interleukin-8 correlate with the release of collagenases, a crucial step that regulates the process of cervical extracellular matrix remodeling. The levels of monocyte chemotactic protein-1; regulated on activation, normal T-expressed and secreted (RANTES); interleukin-8; and growth-regulated oncogene- are elevated in the peritoneal fluid of women with endometriosis, and they correlate with the stage of the disease.

Conclusion(s): Chemokines play a relevant role in many physiologic and pathologic situations, such as ovulation, menstruation, implantation, cervical ripening and preterm labor, and endometriosis. Their regulation soon may provide new therapeutic strategies.     

Elevated C-reactive protein and pro-inflammatory cytokines in Andean women with pre-eclampsia.

OBJECTIVE: To investigate the concentration of markers of inflammation in non-pregnant women, women with normal pregnancy and women with pre-eclampsia. METHODS: Pregnant women (n=26), women with pre-eclampsia (n=25) and non-pregnant normotensive women (n=21) were included in the study. C-reactive protein was measured by latex-enhanced immunoturbidimetric assay, serum tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) by high sensitivity ELISA. Kruskal-Wallis non-parametric analysis of variance followed by the Mann-Whitney U-test were used for statistical analyses. RESULTS: Higher values (mean+/-S.E.M.) of C-reactive protein were found in pre-eclampsia (4.11+/-0.37 mg/dl) compared with normal pregnant women (2.49+/-0.26 mg/dl) and non-pregnant controls (1.33+/-0.15 mg/dl). TNF-alpha was significantly higher in women with pre-eclampsia (15.74+/-5.09 pg/ml), in relation to the control group (2.76+/-0.41 pg/ml) and women with normal pregnancy (8.31+/-1.55 pg/ml). IL-6 levels were significantly higher in pre-eclamptic women (12.91+/-1.29 pg/ml) compared with normal pregnant (5.07+/-0.423 pg/ml) and control women (1.25+/-0.13 pg/ml). CONCLUSIONS: The results of this cross-sectional study in a high-risk Andean population show that both C-reactive protein and pro-inflammatory cytokines are present in higher concentrations in women with pre-eclampsia. The study was undertaken in women with established pre-eclampsia and it is not possible to determine whether the increased concentrations of C-reactive protein and pro-inflammatory cytokines were a cause or consequence of the disease.     

High serum levels of interleukin-6 in endometrial carcinoma are associated with uterine serous papillary histology, a highly aggressive and chemotherapy-resistant variant of endometrial cancer

PURPOSE: To evaluate and compare autocrine expression and production of interleukin-6 (IL-6), a pleiotropic cytokine involved in the resistance to cytotoxic agents and inhibition of anti-tumor immune function in endometrial carcinoma in vitro as well as in vivo. PATIENTS AND METHODS: IL-6 gene expression levels were evaluated in twenty-four primary endometrial tumors including 14 endometrioid carcinomas (EC) and 10 uterine serous papillary carcinoma (USPC) as well as in normal control endometrial cells (NEC) by real-time PCR. Secretion of IL-6 protein by 6 primary endometrial tumor cultures including USPC and EC was measured using a sensitive enzyme-linked immunosorbent assay (ELISA) in vitro. Finally, IL-6 concentration in 71 serum samples including 20 apparently healthy women, 19 women with benign abdominal diseases, 19 women with primary EC, and 13 USPC patients was studied. RESULTS: IL-6 gene expression levels were significantly higher in USPC when compared to EC (mean copy number by RT-PCR = 313 +/- 55 vs. 53 +/- 11, USPC vs. EC, respectively: P < 0.01). IL-6 serum concentrations between normal healthy females (range 0.01-21.23 pg/ml; mean 3.1 pg/ml) and benign disease patients (range 0.01-95.77 pg/ml; mean 13.07 pg/ml) were not statistically different. In contrast, significantly higher levels of IL-6 were detected in both patients with EC (range 2.86-82.13 pg/ml; mean 20.43 pg/ml) and patients with UPSC (range 16.3-500.1 pg/ml; mean 125.7 pg/ml) when compared to the healthy females (P < 0.01), with a mean serum IL-6 level in USPC patients 6.1-fold higher when compared to EC patients (P < 0.03). Accordingly, higher levels of IL-6 secretion were noted in primary USPC cell lines (mean 3121 pg/ml, range between 1099 and 5017 pg/ml/10(5) cells/48 h) when compared to primary EC (mean 88, range between 19 and 112 pg/ml/10(5) cells/48 h) (P < 0.01) in vitro. CONCLUSIONS: IL-6 is highly expressed in USPC, and it is released in high concentration in the serum of USPC patients. IL-6 may be a novel biomarker for USPC. Drugs used to inhibit the expression of IL-6 or the IL-6 signal transduction pathway may potentially be highly beneficial in USPC.     

Increased IL-6 and IL-8 levels in cervicovaginal secretions of patients with cervical cancer.

OBJECTIVE: Conflicting data exist on IL-6 production by human papillomavirus (HPV) immortalized cell lines and several cervical carcinoma cell lines. However, no information has been reported on the levels of cytokines in cervicovaginal washings in relation to cervical neoplasia. The aim of this study was to investigate whether local production of IL-6 could be found and whether the level of this cytokine was related to the severity of cervical neoplasia. IL-8 was measured to obtain additional information on an inflammatory cytokine with possible epithelial origin. METHODS: Cervicovaginal washings and sera were obtained from 35 patients with invasive cervical cancer, 62 patients with cervical intraepithelial neoplasia (CIN), and 25 control subjects. IL-6 and IL-8 levels were determined by ELISA. HPV DNA in cervical smears was detected by a HPV-16-specific PCR method and additionally by CPI/IIG PCR. Histological analysis of the inflammatory infiltrate was performed on hematoxylin-eosin-stained tissue sections. RESULTS: In the patients with cervical cancer, those with CIN, and the controls, the median IL-6 concentration in cervicovaginal washings was 171 pg/ml (interquartile range: 54-780), 22 pg/ml (<2-73), and < 2 pg/ml (<2-<2), respectively. For IL-8, the levels were 2756 pg/ml (1651-7107), 489 pg/ml (248-1158), and 631 pg/ml (346-897), respectively. In most subjects the local levels were much higher than in serum. Local IL-6 and IL-8 levels were significantly higher in patients with cervical carcinoma compared with CIN patients and controls. Likewise, local IL-6 levels were increased in patients with CIN compared with controls. No relation was found between cytokine levels and CIN grade or between cytokine levels and the inflammatory infiltrate scored by histological analysis. CONCLUSIONS: There is local production of IL-6 and IL-8 in cervicovaginal secretions, and the production of IL-6 was related to the severity of cervical neoplasia.     

Monocyte chemotactic protein-2 and -3 in amniotic fluid: relationship to microbial invasion of the amniotic cavity, intra-amniotic inflammation and preterm delivery

OBJECTIVE: To evaluate the presence of monocyte chemotactic protein (MCP)-2 and MCP-3 in cervical and amniotic fluid in women in preterm labor. STUDY DESIGN: Cervical and amniotic fluid was sampled from women with singleton pregnancies (< or =34 weeks) in preterm labor (n = 58). RESULTS: Monocyte chemotactic protein-2 (range: 80-583 pg/ml) and MCP-3 (range: 36-649 pg/ml) were detectable in 7/58 women in preterm labor. Monocyte chemotactic protein-3 was found significantly more often in amniotic fluid of women delivered within 7 days (P < 0.001), <34 weeks (P = 0.002), or with intra-amniotic inflammation (P < 0.001) and microbial invasion of the amniotic fluid (P = 0.003). Women in preterm labor had detectable levels of MCP-2 significantly more often if they gave birth before 34 weeks of gestation (P = 0.038) or had intra-amniotic inflammation (P = 0.042). CONCLUSIONS: The presence of MCPs in amniotic fluid of women in preterm labor was associated with preterm birth before 34 weeks of gestation (MCP-2 and MCP-3), microbial invasion (MCP-3), and inflammation (MCP-2 and MCP-3) of the amniotic cavity.     

Maternal serum cytokine levels in pregnancies complicated by PROM

OBJECTIVE: The aim of the study was to evaluate the maternal serum cytokines levels in pregnancies complicated by premature rupture of membranes (PROM). MATERIALS AND METHODS: Maternal serum of IL-1 beta, IL-4, IL-6, IL-8 and TNF-alfa levels were assessed in patients with PROM between 24-34 weeks of pregnancy (n = 45). Control group consisted of healthy pregnant women (n = 41) at 24-34 weeks of gestation. Serum cytokines concentrations were measured by commercial available enzyme-linked immunosorbent assays. C-reactive protein level and WBC were estimated in both groups. RESULTS: Compared to healthy pregnant, the group of patients with PROM had significantly higher serum levels of IL-1 beta (0.76 pg/ml vs 0.41 pg/ml, p = 0.022), TNF-alfa (1332.46 pg/ml vs 58.01 pg/ml, p < 0.00001) and IL-8 (15.79 pg/ml vs 0 pg/ml, p < 0.00001). CRP concentration and WBC were also significantly higher in serum of pregnant women with PROM then in healthy ones (CRP: 10 mg/l vs 0 mg/l, p = 0.043; WBC: 13,188 +/- 3625/mm3 vs 9132 +/- 1913/mm3, p < 0.00001). No significant differences in IL-6 and IL-4 levels were found between groups. CONCLUSION: Differences in serum maternal levels of cytokines between patients with premature ruptures of membranes and healthy pregnant women suggest that reasons and/or consequences of PROM results in changes in immunological system.     

Amniotic fluid glucose and cytokines values in the early diagnosis of amniotic infection in patients with preterm labor and intact membranes

Objective: Our goal was to compare sensitivity, specificity, and predictive values of glucose and cytokines [interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor (TNF)] in amniotic fluid (AF) to detect an AF-positive culture.

Methods: Amniocentesis was performed on 113 patients with preterm labour (PTL) and intact membranes. Fluid was cultured for aerobic and anaerobic bacteria, and for mycoplasmas. AF analysis included cytokines and glucose determinations.

Results: The prevalence of positive AF cultures was 11.5% (13/113). Anaerobic bacteria were isolated in 9 patients (69.2%). The glucose < 16 mg/dl and cytokines values; IL-1 >640 pg/ml, IL-6 >55,000 pg/ml, IL-8 >1,000 pg/ml, TNF >672 pg/ml, were significantly correlated (P< 0.01) with AF culture result. Glucose had a sensitivity of 69.2% and a specifity of 96% for the prediction of positive AF culture. The sensitivity and specifity of the cytokines ranged from 61.5–53.4% and 79.8–8.99%, respectively.

Conclusions: In the diagnosis of the AF-positive culture, glucose > 16 mg/dl is more sensitive than cytokines.     

子宫内膜异位症病灶分泌的细胞因子与腹腔液微环境关系的研究

目的探讨子宫内膜异位症(内异症)病灶分泌的细胞因子与腹腔液之间的关系及其对生殖的影响.方法对因内异症进行手术治疗或不孕症行腹腔镜检查的妇女43例,其中内异症24例(内异症组)及正常盆腔19例(对照组),采用单核细胞趋化实验分析、斑点杂交分析、酶链免疫吸附测定及胞浆游离钙浓度([Ca2+]i)测定等方法,测定两组患者的腹腔液、腹腔巨噬细胞及异位内膜细胞的特性,并比较两组腹腔液及异位内膜细胞对精子活动力及鼠胚胎卵裂率的影响.结果内异症组及对照组患者腹腔液趋化单核细胞移动的距离分别为(87.2±9.4) μm、(51.9±3.7) μm,两组比较,差异有极显著性(P<0.01);腹腔巨噬细胞数分别为(1.47±0.87)×106/ml、(0.67±0.73)×106/ml(P<0.01);异位内膜细胞可表达低水平的单核细胞趋化蛋白(MCP)-1[吸光度(A)值为18.34±3.95],经白细胞介素(IL)-1β及肿瘤坏死因子(TNF)-α刺激后,其分泌MCP-1mRNA A值分别为56.84±3.21、41.58±2.48,刺激前后比较,差异有极显著性(P<0.01);内异症组腹腔液及异位内膜细胞明显抑制精子的活动力和鼠胚的发育.结论异位症病灶与腹腔液微环境相互影响,腹腔巨噬细胞和异位症病灶合成及分泌某些细胞因子的能力增强,同时可干扰生殖过程的某些环节.     

Selected cytokines and glycodelin A levels in serum and peritoneal fluid in girls with endometriosis

Aim: The aim of this study was to determine the role of serum and peritoneal interleukin (IL)-6, tumor necrosis factor (TNF)-α and glycodelin A levels as diagnostic markers of endometriosis in adolescent girls. Material and Methods: The study encompassed 50 adolescent girls, aged 13-19?years, after menarche and with chronic pelvic pain who qualified for diagnostic laparoscopy. The patients were allocated into two groups: group I (endometriosis group) consisted of subjects with diagnosed endometriosis (n?=?33, 66%) and group II (control group) included those whose laparoscopic examinations revealed no evidence of endometriosis (n?=?17, 34%). IL-6, TNF-α and glycodelin A concentrations in serum and peritoneal samples were assessed using commercially available human enzyme-linked immunosorbent assay kits. The value of P?相似文献   

Spontaneous and stimulated secretion of monocyte chemotactic protein-1 and macrophage migration inhibitory factor by peritoneal macrophages in women with and without endometriosis

OBJECTIVE: To assess spontaneous and stimulated secretion of monocyte chemotactic protein-1 (MCP-1) and macrophage migration inhibitory factor (MIF) by peritoneal macrophages in women with and without endometriosis. DESIGN: Macrophages were isolated from the peritoneal fluid and cultured for different periods of time (6, 20, and 44 hours) without any stimulation to determine spontaneous secretion of MCP-1 and MIF. Macrophages were also exposed to 1 microg/mL lipopolysaccharide for 6 hours to evaluate the stimulated secretion of these cytokines. SETTING: Gynecology clinic and human reproduction research laboratory. PATIENT(S): Twelve fertile women and 11 women with endometriosis. INTERVENTION(S): Peritoneal fluid obtained at laparoscopy. MAIN OUTCOME MEASURE(S): Monocyte chemotactic protein-1 and MIF concentrations in the culture medium using ELISA. RESULT(S): Peritoneal macrophages of women with endometriosis demonstrated an increased capacity to secrete MCP-1 either spontaneously or after stimulation with lipopolysaccharide. They also showed a marked tendency for an increased secretion of MIF, but no statistically significant difference was found. CONCLUSION(S): Monocyte chemotactic protein-1 and MIF production by peritoneal macrophages may contribute to paracrine and autocrine activation and to macrophage accumulation in the peritoneal cavity of women with endometriosis. These mechanisms may exacerbate peritoneal inflammation and favor the growth of endometrial implants.