Mouse embryo toxicity of IL-6 in peritoneal fluids from women with or without endometriosis

BACKGROUND: To determine whether there is a factor (or factors) in the peritoneal fluid of endometriosis patients that impairs embryo growth and embryo implantation. METHODS: Growth and development of two-cell mouse embryos which were cultured in media with peritoneal fluid from women with or without endometriosis and interleukin-1-beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels in conditioned media were measured. RESULTS: The blastocyst rate in the non-endometriosis group was 46.4 +/- 31.1%, and that of the endometriosis group was 54.6 +/- 28.7%. Logistic regression analysis using the criteria of blastocyst development in 454 embryos, showed that the peritoneal fluid from endometriosis could promote (p=0.015) but IL-6 could arrest embryo growth to blastocyst (p=0.025). IL-1beta and TNF-alpha levels had no significant effect on blastocyst formation. CONCLUSION: Peritoneal fluid from women with endometriosis was not toxic to mouse embryo development. However, IL-6 in the peritoneal fluid deteriorated the growth and development of mouse embryos.     

子宫内膜异位症患者腹腔液肿瘤坏死因子α和白细胞介素6的？…

子解子宫内膜内异症患者腹腔液肿瘤坏死因子α和白细胞介素６（ＩＬ－６）水平的变化及对人精子活动力和鼠胚胎发育的影响。方法将行诊断性腹腔镜检查的不孕患者２５例,根据术后诊断分为内异症组（１４例）和对照组（１１例,盆腔正常）,利用双抗体夹心法检测其腹腔液和腹腔巨噬细胞培养上清液中ＴＮＦ－α和ＩＬ－６和水平。并将两组的腹腔液分别与人精子和鼠２细胞期胚进行体外培养,观察萁 上人精子活动力鼠２细胞期胚胎发育的     

子宫内膜异位症患者血清与腹腔液中肿瘤坏死因子α及白细胞 …

目的 了解子宫内膜异位症（内异症）患者血清及腹腔液中肿瘤坏死因子α（ＴＮＦ－α）、白细胞介素６（ＩＬ－６）的水平以及在腹腔镜保守性手术治疗后的变化。方法 收集内异症Ｉ、Ⅱ期及Ⅲ、Ⅳ期患者各１０例（共２０例）有腹腔镜手术前后的血清和腹腔液,并以经腹腔镜检查确诊为与内异症无关病例１０例（共２０例）有腹腔镜手术前后的血清和腹腔液,并以经腹腔镜检查确诊为与内异症无关病例１０例为对照,应用放射免疫双抗体夹心     

达那唑体外对子宫内膜异位症患者腹腔巨噬细胞释放细胞因子 …

目的 了解达那唑体外对子宫内膜异位症（内异症）患者腹腔巨噬细胞释放细胞因子的影响及与胞浆游离钙（「Ｃａ＾２＋」）浓度的关系。方法 将浓度分别为１０μｇ／Ｌ、１００μｇ／Ｌ、１０００μｇ／Ｌ的达那唑加入１４例内异症不孕患者和１１例盆腔正常的不孕患者（对照）的腹腔液中进行培养，用双抗体夹心法检测腹腔巨噬细胞培养上清液中肿瘤坏死因子α（ＴＮＦ－α）和白细胞介素６（ＩＬ－６）的水平。同时，应用Ｆｒｕａ２测     

Peritoneal fluid cytokines and sICAM-1 in minimal endometriosis: search for discriminating factors between infertility and/or endometriosis

OBJECTIVE: To evaluate cytokine levels (IL-1beta, TNF-alpha, IL-6, IL-8), soluble intercellular adhesion molecule-1 (sICAM-1) and number of macrophages in peritoneal fluid (PF) of women with no minimal endometriosis and associated (or not) infertility in order to discriminate between infertility and/or endometriosis. STUDY DESIGN: Cytokines and sICAM-1 were measured by using quantitative enzyme-linked immunosorbent assay (ELISA) while the macrophages were identified by May-Grunwald-Giemsa and non-specific esterase staining and presented as medians. The measurements were performed in 78 women belonging to four selected subgroups according to their endometriosis and/or infertility status. Statistical analysis was performed using Kruskal-Wallis non-parametric ANOVA test. Additionally, discriminant function analyses were performed. RESULTS: We have found the most elevated macrophage numbers in the groups of women with endometriosis. IL-1beta did not present any statistically significant values differentiating the analysed subgroups. IL-6 (110.0 pg/ml) and TNF-alpha exhibited the highest concentrations (statistically significant) in a group of fertile women with endometriosis. IL-8 clearly differentiated between the subgroups with infertility and sICAM-1 was statistically significantly elevated in the subgroups of infertile women. In the forward discriminant analysis, when subdividing the studied population according to its infertility status (we considered macrophages, IL-8 and IL-6 in order of probability values), we have found striking probability value of 92% for the correct classification into an infertile population. CONCLUSION: Out of the range of the analysed factors we have found only the sICAM-1 to be singled out between the standard discriminant analysis and the forward one. However, this important flagging molecule might be of considerable value for discrimination between different types of pathology at the level of immune effector function. The increased levels of TNF-alpha and IL-6 signified a group of fertile women with endometriosis; however only IL-6 presented a discriminating value in multifunctional analysis of examined subgroups. The analysed range of factors had a greater tendency to discriminate between infertility status rather than endometriosis.     

Differential flow cytometric detection of intracellular cytokines in peripheral and peritoneal mononuclear cells of women with endometriosis

OBJECTIVE: The pathogenesis of endometriosis is related to functional changes in CD3+ and CD14+ cells observed both at the local and systemic level. Here we investigated whether, and if so, how the body compartment influences cytokine expression in stimulated peritoneal and peripheral CD3+ and CD14+ cells of women with endometriosis. STUDY DESIGN: Isolated peripheral blood (PB) and peritoneal fluid (PF) mononuclear cells from women with endometriosis were cultured under non-adherent conditions and stimulated with PMA and ionomycin for 6h to induce intracellular cytokine synthesis of TNF-alpha, IFN-gamma, and IL-8 by CD3+ cells or with LPS for 9h to produce TNF-alpha, IL-6, IL-10, MCP-1, and IL-8 by CD14+ cells. RESULTS: The percentages of positive CD3+ cells stained for TNF-alpha and IFN-gamma were significantly higher and those stained for IL-8 were significantly lower in PF compared with PB, this being independent of the stage of endometriosis. In contrast, the percentages of CD14+ cells producing TNF-alpha, IL-6, IL-10, MCP-1, and IL-8 were significantly higher in PB than PF of women with endometriosis. CONCLUSIONS: Monocytes/macrophages and lymphocytes derived from the peripheral and peritoneal compartments of women with endometriosis differentially respond to stimulated cytokine synthesis induction. However, it is difficult to state whether the observed phenomenon is more related to body compartment influence per se or to the presence of endometriosis.     

The G(-2518)A polymorphism of monocyte chemotactic protein-1 (MCP-1) and its serum and peritoneal fluid levels in Korean women with endometriosis

OBJECTIVES: To investigate the associations between endometriosis and the G(-2518)A polymorphism of monocyte chemotactic protein-1 (MCP-1), and serum and peritoneal fluid MCP-1 levels in Korean women. STUDY DESIGN: The G(-2518)A polymorphism of MCP-1 was analyzed by restriction fragment length polymorphism in 105 women with and in 101 women without endometriosis. Serum and peritoneal fluid MCP-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The genotype frequencies of the MCP-1 G (-2518)A polymorphism were GG 36.9%, AG 52.9%, and AA 10.2%. MCP-1 genotype frequencies and serum and peritoneal fluid MCP-1 levels were similar in those with or without endometriosis and were not dependent on disease stage. A significant correlation was found between serum and peritoneal fluid levels of MCP-1. However, no differences were found between MCP-1 genotypes in terms of serum and peritoneal fluid MCP-1 levels. CONCLUSIONS: Serum and peritoneal fluid MCP-1 levels and the G (-2518)A MCP-1 polymorphism were found not to be associated with endometriosis in Korean women.     

Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis

Endometriosis is a disorder characterised by presence and growth of endometrial tissue outside the uterus, primarily into the peritoneum. The peritoneal fluid (PF) of women with endometriosis undergoes a number of biological changes, including local inflammatory-reparative phenomena and peripheral blood mononuclear cells (PBMC) involvement. These activated cells as well as the endometriotic cells secrete various cytokines with pleiotropic biological activities. Dynamic interplay among cytokines may contribute to realise a favourable microenvironment for the implantation of endometrial cells and the progression of the disease. In the present study, we evaluated the levels of cytokines, such as the tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) in PF and in serum (S) of women with endometriosis to compare their behaviour in both biological fluids. The patients (n = 26) were women of reproductive age attending our observation centre for infertility, diagnosed endometriosis at laparoscopy. Control group (n = 5) consisted of women affected by non-immunologic infertility, diagnosed by explorative laparoscopy. S samples were obtained from peripheral blood before anaesthesia and laparoscopy. PF samples were collected at the time of laparoscopy. Both biological fluids were examined for cytokine by ELISA assays. Our results showed that S and PF levels of TNF-alpha, not dosable in controls, were very high at the early stage and decreased significantly with the severity of the disease (p < 0.001). TGF-beta levels were significantly (p < 0.001) higher than in controls and increased with the severity of the disease (p < 0.001), particularly in the PF. S and PF IL-8 as well as MCP-1 concentrations at all stages were higher than in controls (p < 0.001), yet showed an opposite behaviour in both biological fluids. In fact, S levels of IL-8 and MCP-1 were significantly (p < 0.001) higher at early stages and decreased with the severity of the disease, whereas we observed a significant (p < 0.001) enhancement of these chemokine levels in PF from stage I to stage II and stage III. These observations showed that TNF-alpha and TGF-beta levels were overlapping in S and PF of women with endometriosis. On the contrary, MCP-1 and IL-8 S concentrations decreased with the severity of the disease, whereas PF levels showed markedly increased at severe stages. Taken together the observed changes may be due both to the increased peritoneal macrophage activity and to the larger recruitment of PBMC and autocrine release by endometriotic cells.     

Serum and follicular fluid levels of soluble Fas and soluble Fas ligand in IVF cycles

OBJECTIVE: To determine follicular fluid (FF) and serum levels of soluble Fas (sFas) and soluble Fas ligand (sFasL) in patients undergoing IVF cycles. STUDY DESIGN: A prospective comparative study among patients with endometriosis (n=12), infertility due to male factor (n=12) and poor responders (n=32) undergoing IVF cycles in Centrum IVF Clinic. Individual FF and serum samples were collected from patients during transvaginal ultrasonography-guided follicle aspiration. Patients were classified as poor responder patients undergoing IVF cycles with GnRHa, triptorelin and GnRH antagonist, cetrotide, patients with endometriosis and patients with infertility due to male factor. sFas, sFasL levels in both FF and serum samples and their correlations with clinical outcomes of IVF were measured in each study group. RESULTS: Serum and FF levels of sFas, sFasL were similar in the poor responder and male factor groups. There were no differences between the serum and FF levels of both sFas and sFasL among poor responder patients receiving either GnRH agonist or antagonist therapies. Serum levels of sFas were significantly lower in the endometriosis group compared to the male factor group. Serum and FF levels of sFas, sFasL were similar among patients with or without clinical pregnancy. CONCLUSION: sFas and sFasL are detected in both serum and follicular fluid samples from IVF cycles, their levels are similar between poor responder and male factor groups as well as between GnRH agonist and antagonist treatment groups. These soluble apoptotic factors may not be predictive for the outcomes of IVF. Decreased serum levels of sFas, suggests increased apoptosis in endometriosis.     

子宫内膜异位症患者辅助性T细胞亚群免疫状态的研究

目的　探讨辅助性T细胞 (Th)亚群在子宫内膜异位症 (内异症 )发病中的作用。方法　采用酶联免疫吸附法检测 30例内异症患者 (内异症组 )及 2 0例非内异症患者 (对照 1组 )血清及腹腔液中白细胞介素 (IL) 2、6的水平 ;用免疫组化技术分别检测IL 2、IL 6在内异症组患者异位内膜组织和 10例子宫肌瘤患者 (对照 2组 )的正常子宫内膜组织中的表达。结果　内异症组患者血清及腹腔液中位数IL 6水平分别为 5 3、2 1ng/L ,对照 1组患者血清及腹腔液中位数IL 6水平分别为 2 5、0 9ng/L ,两组妇女血清和腹腔液中IL 6水平分别比较 ,差异均有统计学意义 (P <0 0 5 ) ;内异症组Ⅲ～Ⅳ期患者血清及腹腔液中位数IL 6水平分别为 13 6、4 1ng/L ,Ⅰ～Ⅱ期患者血清及腹腔液中位数IL 6水平分别为 3 7、1 6ng/L ,Ⅲ～Ⅳ期患者与Ⅰ～Ⅱ期患者血清及腹腔液中位数IL 6水平比较 ,差异均有统计学意义 (P <0 0 5 ) ;内异症组IL 2 /IL 6比值在血清及腹腔液中分别为 0 7、1 1,均分别低于对照组的 0 8、6 2 ,差异也有统计学意义 (P <0 0 5 )。内异症组患者腹腔液与血清IL 6水平呈正相关 (r =0 74 5 ,P <0 0 1) ,血清及腹腔液中IL 6水平与IL 2 /IL 6比值均呈负相关 (r =- 0 4 0 6 ,P <0 0 5 ;r =- 0 4 80 ,P <0 0 5 )     

Serum cytokines as biomarkers for nonsurgical prediction of endometriosis

OBJECTIVE: To test the ability of a group of serum cytokines, either individually or in combination, to serve as biomarkers for the nonsurgical diagnosis of endometriosis. STUDY DESIGN: Subjects were allocated to two groups according to their laparoscopic diagnosis. The first group consisted of patients with endometriosis and the second group was made up of infertile women with no pelvic pathology (controls). Blood samples were collected preoperatively and stored. Cytokines were measured in the serum of all participants using the Bio-Plex Protein Array System. Nonparametric statistics and the Mann-Whitney test were used to compare groups. Subjects were seen at the Gynecologic endoscopy unit. RESULTS: Three cytokines were significantly higher in the serum of subjects with endometriosis than in the control group: interleukin-6 (IL-6) [4.41 pg/ml (range: 1.47-15.01) versus 0.97 pg/ml (range: 0.29-2.98), respectively; p<0.001], monocyte chemotactic protein-1 (MCP-1) [37.91 pg/ml (range: 24.54-94.74) versus 22.13 pg/ml (range: 13.85-39.45), respectively; p<0.001], and interferon-gamma (INF-gamma) [19.01 pg/ml (range: 1.19-73.52) versus 0.30 pg/ml (range: 0.00-13.05), respectively; p<0.001]. There was no statistically significant difference between subjects with endometriosis and controls in the serum concentration of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), or granulocyte macrophage colony stimulating factor (GM-CSF). Interleukin-2 (IL-2), interleukin-8 (IL-8), and interleukin-15 (IL-15) were undetectable in the serum of both groups. None of the measured cytokines showed significant correlation with the cycle phase or stage of endometriosis. In a multivariate analysis, serum interleukin-6 provided a sensitivity of 71% and a specificity of 66% to discriminate between endometriosis patients and controls at a cutoff point of 1.9 pg/ml. Adding monocyte chemotactic protein-1 and interferon-gamma to interleukin-6 did not increase the discriminative ability over that achieved by measuring serum interleukin-6 alone. CONCLUSIONS: Serum of subjects with endometriosis contains significantly higher levels of interleukin-6, monocyte chemotactic protein-1, and interferon-gamma than control women. Serum interleukin-6 measurements discriminate between women with endometriosis and controls. Interleukin-6 provides a promising serum marker for the nonsurgical prediction 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。     

Serum and peritoneal fluid levels of interleukin-6 and interleukin-37 as biomarkers for endometriosis

This study aimed to compare the levels of interleukin (IL)-1β, IL-6, IL-10, and IL-37 in the serum and peritoneal fluid of women with and without endometriosis. In addition, it aimed to determine the diagnostic values of the cytokines with significantly different concentrations. The levels of IL-1β, IL-6, IL-10, and IL-37 in the serum and peritoneal fluid samples of 40 women with endometriosis and 32 women without endometriosis were measured using an enzyme-linked immunosorbent assay. The serum and peritoneal fluid levels of IL-1β and IL-10 were not statistically significantly different between the endometriosis and control groups. The IL-6 and IL-37 levels in the serum and peritoneal fluid were higher in the endometriosis group than in the control group, and they were correlated with the stage of endometriosis. The AUC for the IL-37 was 0.897 for the serum and 0.934 for the peritoneal fluid, while the AUC for the IL-6 was 0.905 for the serum and 0.952 for the peritoneal fluid. Our results suggest that the serum and peritoneal fluid IL-6 and IL-37 levels were significantly increased in the endometriosis patients, indicating that these cytokines may serve as biomarkers for the diagnosis of endometriosis.     

Vascular endothelial growth factor and interleukin-6 in peritoneal fluid of women with endometriosis

OBJECTIVE(S): To determine [1] vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) levels in peritoneal fluid from women with endometriosis and compare them with those from oral contraceptive (OC) users and normal cycling women and [2] any correlation between VEGF and IL-6 concentrations. DESIGN: Controlled clinical study. SETTING: University medical center. PATIENT(S): Patients undergoing laparoscopy for infertility or other benign gynecologic conditions. INTERVENTION(S): Peritoneal fluid samples were collected. MAIN OUTCOME MEASURE(S): Levels of VEGF and IL-6 in peritoneal fluid were determined. RESULT(S): Compared with normal controls or women with less severe endometriosis (implant scores of 5 or less), women with more advanced endometriosis (implant scores of 6 or more) have elevated VEGF and IL-6 levels in peritoneal fluid. Compared with normal controls, markedly suppressed IL-6 but similar VEGF levels were found in peritoneal fluid from OC users. Neither VEGF nor IL-6 varied cyclically in normal women or those with endometriosis. There was no correlation between levels of VEGF and IL-6 in peritoneal fluid. There was no correlation between implant scores and VEGF or IL-6 levels. CONCLUSION: The inflammation associated with endometriosis, through increased levels of peritoneal fluid VEGF, may promote angiogenesis for the progressive growth of endometriosis. Effective treatment of endometriosis by combination estrogen-progestin pills may involve the suppression of such inflammatory responses.     

Cytokine profiles in autologous peritoneal fluid and peripheral blood of women with deep and superficial endometriosis

In a preliminary study the hypothesis was tested that cytokine profiles in peripheral blood were higher in women with deep infiltrating endometriosis and cytokine profiles in peritoneal fluid were higher in women with superficial endometriosis. Thirteen women of reproductive age having laparoscopy for infertility (n=9), pain (n=3) or combined pain and infertility (n=1). Peripheral blood and peritoneal fluid were obtained and analyzed for Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-10 (IL-10), Transforming Growth Factor-betal (TGFβ1), and Interferon-gamma (IFN-γ). No significant cytokine differences were observed in either peritoneal fluid or peripheral blood between IL-6, TGFβ1, IFNγ, TNF-alpha and IL-10 of women with superficial endometriosis (n=7) and women with deeply infiltrating endometriosis (n=6). The results of this preliminary study do not show significant differences in peripheral blood and peritoneal fluid cytokine levels between women with deep infiltrating endometriosis compared to women with superficial disease. Future studies with increased sample size are required to either confirm or refute these preliminary findings. Received: 5 January 2000 / Accepted: 14 August 2000     

Comparison of cytokine levels and embryo toxicity in peritoneal fluid in infertile women with untreated or treated endometriosis.

OBJECTIVE: Our aim was to examine the relationship between the levels of cytokines in peritoneal fluid and its embryo toxicity. STUDY DESIGN: The levels of interleukin-1 and tumor necrosis factor were measured in peritoneal fluid from infertile women who did not have endometriosis (n = 21), who had untreated endometriosis (n = 19), and who had undergone medical treatment for endometriosis (n = 10). Embryo toxicity was investigated in mouse two-cell embryos cocultured with the oviducts in culture media that contained various concentrations of peritoneal fluid. RESULTS: The levels of cytokines were significantly higher in the peritoneal fluid from women who had untreated endometriosis than in women who did not have endometriosis, but they were extremely low in women who had undergone medical treatment with either danazol or buserelin. The peritoneal fluid from women who had untreated endometriosis adversely affected the cleavage of mouse two-cell embryos. After medical treatment the embryo toxicity of the peritoneal fluid was almost undetectable. CONCLUSION: These results offer some theoretic bases in support of medical treatment to improve reproductive performance in infertile women who have endometriosis.     

Role of cytokines in endometriosis-associated infertility

Endometriosis, which is common in women of reproductive age, may affect fertility. It is also clear that mechanical disruption of the pelvic anatomy may cause infertility. However, our understanding of the association between the early stage of endometriosis and infertility remains incomplete. Bloody peritoneal fluid (PF) is frequently observed in the cul-de-sac of endometriosis patients and contains various biologically active factors. We found that the concentrations of tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) in PF from patients with endometriosis were significantly higher than that of patients with endometriosis. There were significantly positive correlations between the levels of TNF-alpha and IL-6. We compared the levels of these cytokines with regard to the R-AFS stages and scores, but no differences were observed. In contrast, these cytokines correlate with the number and extent of red color peritoneal endometriosis. TNF-alpha increased the expression of IL-6 messenger RNA and protein in endometriotic stromal cells derived from chocolate cyst in a dose-dependent manner. The addition of IL-6 inhibited the development of mouse preimplantation embryo and impaired sperm function. We concluded that increased levels of IL-6 in peritoneal fluid of patients with active red endometriosis might be related to endometriosis-associated fertility.     

Peritoneal fluid cytokine and eicosanoid levels and their relation to the incidence of peritoneal adhesion.

OBJECTIVE: To determine the peritoneal fluid content of several cytokines and eicosanoids with inflammatory, anti-inflammatory, anti-fibrotic, and fibrotic activities, and to assess the relationship of these levels with the incidence of peritoneal adhesions. METHODS: Peritoneal fluids were collected from 30 subjects with adhesions (n = 22) or with normal pelvic anatomy (n = 8), and the level of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), interleukin-10 (IL-10), interferon gamma (IFN-gamma), transforming growth factor beta-1 (TGF-beta 1), granulocyte macrophage-colony stimulating factor (GM-CSF), prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and thromboxane B2 (TXB2) were determined by enzyme-linked immunosorbent assay (ELISA) and radioreceptor assay. RESULTS: The peritoneal fluid content of these factors varied considerably, with low levels of IL-1 beta, TNF-alpha, IL-10, IFN-gamma, and GM-CSF. Only IFN-gamma levels were significantly lower in subjects with adhesions compared with the normal group (P < .05). The levels of total (latent + active) and active TGF-beta 1 were higher than those of other cytokines assayed and were significantly higher in subjects with adhesions compared with the normal group (P < .05). The peritoneal fluid content of PGE2, TXB2, and LTB4 was significantly higher than that of the cytokines and was higher, but not significantly so, in subjects with adhesions compared with normal subjects (P = .06). CONCLUSION: Although the effect of length of time since the adhesions were formed is not known, the results indicate that peritoneal fluid content of these cytokines and eicosanoids, with the exception of IFN-gamma and TGF-beta 1, does not correlate with the presence of peritoneal adhesions.     

Cytokine mapping of sera from women with preeclampsia and normal pregnancies

INTRODUCTION: Preeclampsia is a pregnancy-specific syndrome. The immune system in preeclampsia is changed with an increased innate activity and there is a hypothesis of a shift towards Th1-type immunity. The aim of this study was to determine a spectrum of soluble immunological factors denoting different aspects of immune activation in third trimester sera from women with preeclampsia (N=15) and compare with levels in sera from normal pregnant women (N=15). MATERIAL AND METHODS: IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12 p40, IL-13, IL-15, IL-17, IFN-alpha, IFN-gamma, TNF-alpha, GM-CSF, MIP-lalpha, MIP-1beta, MCP-1, eotaxin and RANTES were measured in serum using multiplex bead arrays. The levels of soluble CD14 and soluble IL-4 receptor were measured by enzyme-linked immunoassay (ELISA). RESULTS: Preeclamptic women had significantly increased levels of circulating IL-6 (p=0.002), IL-8 (p=0.003) and soluble IL-4R (p=0.037), compared to women with normal pregnancies. CONCLUSION: This study supports the hypothesis of increased inflammatory responses in preeclampsia, illustrated by the increased levels of IL-6 and IL-8. The finding of increased levels of soluble IL-4 receptor is an intriguing finding with several interpretations, which may partly support the hypothesis of a Th1 shift in preeclampsia.     

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.