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.     

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.     

Decreased peritoneal concentrations of interleukin-15 in women with advanced stage endometriosis

OBJECTIVE: To assess the concentrations of interleukin-15 (IL-15) in peritoneal fluid from women with endometriosis and fertile disease-free controls. STUDY DESIGN: Peritoneal fluid samples were obtained from 50 women with endometriosis and 29 fertile women having tubal ligation. Concentrations of IL-15 were measured. RESULTS: The mean (S.D.s) concentration of IL-15 in peritoneal fluid was 11.17 pg/mL (3.89) for women with endometriosis, and 12.59 pg/mL (4.11) for fertile disease-free controls. The difference of peritoneal IL-15 concentrations between endometriosis and control women was not statistically significant. However, peritoneal IL-15 concentrations were significantly lower in women with moderate/severe endometriosis when compared with those in women with minimal/mild endometriosis, and in controls (P<0.05). In addition, peritoneal IL-15 concentrations did not correlate with the phase of menstrual cycle in endometriosis or control women. CONCLUSIONS: Our results suggest that the decreased peritoneal IL-15 concentrations in women with moderate/severe endometriosis imply a role of IL-15 in the pathogenesis of advanced endometriosis as compared to those with minimal/mild endometriosis and fertile disease-free controls.     

Elevated soluble Fas ligand levels may suggest a role for apoptosis in women with endometriosis

OBJECTIVE: To evaluate soluble Fas ligand concentrations in serum and peritoneal fluid from women with endometriosis and from fertile controls without endometriosis, and to study levels of soluble Fas ligand in conditioned media of cultured endometrial stromal cells. DESIGN: Prospective, experimental trial. SETTING: Two academic IVF centers. PATIENT(S): Twenty-nine fertile women without endometriosis and 57 infertile women with endometriosis (32 with stage I or II disease and 25 with stage III or IV disease). MAIN OUTCOME MEASURE(S): Enzyme-linked immunosorbent assay was used to measure soluble Fas ligand concentrations in paired samples of serum and peritoneal fluid from women with and without endometriosis. Concentrations were also measured in conditioned media of cultured endometrial stromal cells at basal conditions and after stimulation with interleukin-8 (0.001-10 ng/mL) and tumor necrosis factor-alpha (1-10 ng/mL). RESULT(S): Compared with fertile controls and women with early-stage of endometriosis, women with moderate to severe endometriosis had elevated serum (87.2 +/- 6.4, 88.2 +/- 6.9, and 162.3 +/- 7.8 pg/mL, respectively) and peritoneal fluid (81.0 +/- 6.0, 80.5 +/- 6.8, and 166.2 +/- 10.3 pg/mL, respectively) concentrations of soluble Fas ligand. Serum levels of soluble Fas ligand positively correlated with levels in peritoneal fluid. Comparison of patients in the same menstrual cycle in each group revealed that increased levels of soluble Fas ligand in patients with advanced endometriosis were not attributable to the difference in cycle phases. Soluble Fas ligand was not detected in conditioned media of endometrial stromal cells under baseline conditions or after stimulation. CONCLUSION(S): Serum and peritoneal fluid of women with moderate to severe endometriosis contain elevated concentrations of soluble Fas ligand compared to women with minimal or mild endometriosis and women without endometriosis. These findings suggest a role for apoptotic dysregulation in the pathophysiology 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.     

Role of cytokines in progression of endometriosis

Peritoneal fluid in women with endometriosis contains an increased number of activated macrophages that secrete a variety of cytokines, including interleukin (IL)-6, IL-8, vascular endothelial growth factor, and tumor necrosis factor-alpha (TNF-alpha). Cytokines may be involved in the control of implantation and the growth of endometrial cells outside the uterus. In addition, several cytokines have been implicated in or directly associated with angiogenic activity in endometriosis. There could be a relationship between the levels of cytokines in the peritoneal fluid of patients with endometriosis and the status of the lesions in such patients. Peritoneal endometriosis can be classified as having red, black, or white lesions. Red lesions are known to be an active form of early endometriosis, because vascularization and mitotic activity are shown to be most prominent in these lesions. We found that the peritoneal fluid levels of TNF-alpha and IL-8 were significantly higher in patients with endometriosis, and correlated with the size and number of active lesions. In addition, TNF-alpha and IL-8 stimulated the growth of ectopic endometrial stromal cells. These cytokines with angiogenic activity may therefore have significant roles in the pathogenesis of endometriosis.     

Altered gene expression and secretion of interleukin-6 in stromal cells derived from endometriotic tissues

OBJECTIVE: To compare the expression of interleukin-6 (IL-6) in endometrial and endometriotic cells. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan. PATIENT(S): Twenty patients who underwent either hysterectomy or laparoscopic surgery. INTERVENTION(S): Endometrial and endometriotic stromal cells were obtained from normal endometrium and from chocolate cyst linings of the ovary. Peritoneal macrophages were isolated from peritoneal fluids. Cells were cultured in the presence or absence of tumor necrosis factor-alpha. MAIN OUTCOME MEASURE(S): Gene expression of IL-6 was examined by Northern blot analysis. Interleukin-6 protein production was examined by immunocytochemical staining and ELISA. RESULT(S): A single IL-6 messenger RNA band of approximately 1.3 kilobases was detected in endometriotic stromal cells. Tumor necrosis factor-alpha increased the expression of IL-6 messenger RNA in endometriotic cells in a dose-dependent manner. In endometrial stromal cells, IL-6 messenger RNA signals were much weaker. Endometriotic stromal cells produced significantly larger amounts of IL-6 compared with endometrial stromal cells under basal conditions and after stimulation with tumor necrosis factor-alpha. Interleukin-6 protein was detected in cells isolated from endometriotic tissues by immunocytochemical staining. Interleukin-6 production by cultured macrophages from patients with endometriosis and endometriotic stromal cells was comparable. CONCLUSION(S): Altered gene expression and protein secretion of IL-6 in patients with endometriosis may contribute to the pathogenesis of the disease and/or to endometriosis-associated infertility.     

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     

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.     

Decreased levels of interleukin-18 in peritoneal fluid but not in serum of patients with endometriosis

OBJECTIVE: To determine the concentrations of interleukin-18 (IL-18) in peritoneal fluid and serum in patients with endometriosis in comparison with the control group. DESIGN: A prospective analytical study. SETTING: The obstetrics and gynecology department of an academic training hospital. PATIENT(S): Forty-four patients who underwent laparoscopic surgery for benign gynecologic diseases. INTERVENTION(S): Specimens of peripheral blood and peritoneal fluid were obtained before and during laparoscopic procedures, and the levels of IL-18 were analyzed. MAIN OUTCOME MEASURE(S): The concentrations of IL-18 in peritoneal fluid and serum were correlated with the presence of endometriosis, disease stage, and the phase of the menstrual cycle. RESULT(S): Interleukin-18 was detectable in 98% of the peritoneal specimens and 84% of the serum specimens of the patients tested. Peritoneal fluid IL-18 concentrations were statistically significantly lower in patients with endometriosis than in patients without endometriosis; the difference in serum IL-18 levels showed no statistically significant difference between the patients with and without endometriosis. The concentrations of IL-18 in peritoneal fluid and serum were not correlated with the stage of endometriosis or the phase of the menstrual cycle. CONCLUSION(S): Our results suggest that the decreased levels of IL-18 in peritoneal fluid in patients with endometriosis as compared with the control group may play an important role in the pathogenesis of this disease.     

Increased ENA-78 in the follicular fluid of patients with endometriosis

BACKGROUND: It is known that endometriosis is an inflammatory disease and those patients seem to have lower pregnancy rates. The aim of the study was to investigate the concentrations of chemokines and proinflammatory cytokines in the follicular fluid of patients with and without endometriosis. METHODS: Follicular aspiration, recovering follicular fluid during assisted reproductive treatment, follicular fluid storage and analysis of chemokines and proinflammatory cytokines were carried out. Tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-8, interleukin-15, leukemia inhibitory factor, epithelial neutrophil-activating peptide 78, regulated upon activation, normal T-cell expressed and secreted, and growth-regulated oncogene-alpha were analyzed in the follicular fluid and compared between women with (n =47) and without endometriosis (n = 279). RESULTS: The above cytokines were detected in the follicular fluid samples. Epithelial neutrophil-activating peptide 78 levels were significantly higher in follicular fluid from endometriosis patients than from controls (p = 0.008). Increases (to twice the control level) were also observed for tumor necrosis factor-alpha and for interleukin-6. CONCLUSIONS: Increased follicular fluid levels of epithelial neutrophil-activating peptide 78, tumor necrosis factor-alpha and interleukin-6 indicate that these cytokines may influence oocyte quality and fecundability of women with endometriosis by deteriorating the microenvironment in the human follicle.     

Peritoneal fluid-mediated enhancement of eutopic and ectopic endometrial cell proliferation is dependent on tumor necrosis factor-alpha in women with endometriosis

OBJECTIVE: To determine the effect of autologous peritoneal fluid and tumor necrosis factor-alpha (TNF-alpha) on proliferation of endometrial cells from women with endometriosis. DESIGN: Endometrial cells from eutopic and ectopic endometrium were cultured in vitro with peritoneal fluids or recombinant TNF-alpha for 72 hours before DNa synthesis determination by 3H-thymidine labeling and liquid scintillation counting. SETTING: An institute for the study and treatment of endometriosis and university-based research laboratories. PATIENT(S): Thirty-five women with endometriosis and 17 controls without endometriosis. MAIN OUTCOME MEASURE(S): In vitro incorporation of 3H-thymidine in endometrial cells was examined. RESULT(S): Peritoneal fluid from women with endometriosis enhanced proliferation of autologous and heterologous endometrial cell cultures from women with endometriosis. The soluble TNF-receptor etanercept blocked the ability of peritoneal fluid from women with endometriosis to enhance proliferation of eutopic or ectopic endometrial cells. Recombinant TNF-alpha also enhanced proliferation of eutopic and ectopic endometrial cells from women with endometriosis. In contrast, autologous peritoneal fluid, heterologous peritoneal fluid from women with endometriosis, and recombinant TNF-alpha failed to enhance, and often inhibited, the proliferation of eutopic endometrial cells from controls without endometriosis. CONCLUSION(S): Endometrial cells from women with endometriosis can utilize factors in peritoneal fluids, such as TNF-alpha, to facilitate proliferation in ectopic environments. Endometrial cells from women without endometriosis do not share this ability, suggesting that this abnormality is etiologically related to development of the disease. Therapy with agents that block the effects of TNF-alpha may be warranted.     

Peritoneal fluid interleukin-6 in women with chronic pelvic pain

OBJECTIVE: To determine the relationship between peritoneal fluid concentrations of interleukin-6 (IL-6) and chronic pelvic pain symptomatology in women with adhesions, endometriosis, or no obvious intraperitoneal pathology. DESIGN: Clinical research study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Reproductive-aged women undergoing laparoscopy for the diagnosis of pelvic pain, infertility, or sterilization were selected. INTERVENTION(S): Peritoneal fluid was collected at the time of the laparoscopy and later assayed for IL-6. Subjects completed a pelvic pain questionnaire, and operative reports were used to obtain the underlying diagnosis. MAIN OUTCOME MEASURE(S): Interleukin-6 concentrations. RESULT(S): No correlation between the presence or absence of pelvic pain, findings of adhesions or endometriosis, and the concentration of peritoneal fluid IL-6 was observed. Conclusion(s): The cytokine IL-6 does not seem to play a role in the genesis of chronic pelvic pain in women with adhesions or endometriosis.     

Peritoneal fluid concentrations of interleukin-17 correlate with the severity of endometriosis and infertility of this disorder

This prospective study aimed to determine whether patients with endometriosis are having different level of interlukin-17 (IL-17) in peritoneal fluid when compared with patients without endometriosis. The patients with minimal/mild endometriosis had a significantly higher level of IL-17 in peritoneal fluid compared with those with moderate/severe endometriosis or without endometriosis. The concentration of IL-17 in peritoneal fluid was significantly higher when endometriosis and infertility coexist. However, the concentration of IL-17 in peritoneal fluid did not correlate with the phase of the menstrual cycle in the patients with or without endometriosis. Our study suggested that IL-17 might play an important role in the pathogenesis of early endometriosis and endometriosis-associated infertility.     

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     

Association of interleukin-6 and estradiol with hepatocyte growth factor in peritoneal fluid of women with endometriosis

BACKGROUND: Different cytokines and ovarian steroid hormones have been reported to regulate the growth and maintenance of endometriosis. We determined the relationship between peritoneal fluid concentrations of interleukin-6, ovarian steroids and hepatocyte growth factor in different revised American Fertility Society (AFS) staging and morphologic appearances of endometriosis. METHODS: Peritoneal fluid was collected from 30 women with endometriosis and 20 women without endometriosis during laparoscopy, and hepatocyte growth factor, interleukin(IL)-6 and ovarian steroids were measured in peritoneal fluid. The concentrations of hepatocyte growth factor and IL-6 in peritoneal fluid were measured by ELISA, and that of estradiol and progesterone by using the immulyze-enzyme amplified luminescence system. Changes in peritoneal fluid concentrations of hepatocyte growth factor, IL-6, estradiol and progesterone in different stages and morphologic appearances of endometriosis were examined to demonstrate their differences in early and advanced endometriosis. RESULTS: Peritoneal fluid levels of hepatocyte growth factor in women with stage I-II endometriosis were significantly higher than in both women with stage III-IV endometriosis and without endometriosis. A similar significant increase in stage I-II endometriosis was also observed for IL-6 and estradiol. When we divided the women according to different morphologic appearances of endometriosis, we found significantly higher concentrations of hepatocyte growth factor (HGF), IL-6, estradiol and progesterone in women containing red lesions compared with other pigments or without endometriosis. A positive correlation was observed between peritoneal fluid levels of IL-6 and hepatocyte growth factor only but not between other markers. Although estradiol levels in peritoneal fluid showed an increased tendency to elevate in the proliferative phase of endometriosis women, hepatocyte growth factor and progesterone displayed higher concentrations in the secretory phase of the menstrual cycle. After adjusting different variables in peritoneal fluid, multiple analysis of covariance indicated that hepatocyte growth factor levels in peritoneal fluid were independently involved in the red morphologic activity of endometriosis. CONCLUSIONS: Early staging and red color appearance of endometriosis are associated with the elevation in peritoneal fluid concentrations of hepatocyte growth factor, IL-6 and estradiol, demonstrating the combined effect of these cytokines and ovarian steroids in the production of hepatocyte growth factor from endometrial tissues in active endometriosis.     

Minimal and mild endometriosis. Nd:YAG laser treatment and changes in prostaglandin concentrations in peritoneal fluid

Among many patients, infertility originates with minimal and mild endometriosis. Recently, peritoneal fluid factors have come to be associated with infertility in minimal and mild endometriosis patients, and prostaglandin (PG) is suspected of being one of those factors. We use the Nd:YAG laser for treatment of endometriosis; a total of 52 cases of minimal and mild endometriosis have been treated so far with the laser under laparoscopy in our clinic. At the same time we measured the peritoneal fluid volume and PG concentration in peritoneal fluid. Peritoneal fluid volume and PGE2 concentrations were found to be significantly higher than those in the control group (tubal obstruction patients). Seven of 52 patients received second-look laparoscopy three months after Nd:YAG laser treatment; the PG concentration showed a tendency to decrease in many patients, and the PGE2 concentration turned out to be insignificant. Within one year, 30 patients achieved pregnancy. In minimal and mild endometriosis patients Nd:YAG laser treatment may alter the PG concentration in peritoneal fluid, thereby increasing the change of pregnancy.     

Lipid peroxides, tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) in peritoneal fluid from infertile women with minimal and mild endometriosis

OBJECTIVES: To assess the concentrations of tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and lipid peroxides (the marker of free radicals activity) in peritoneal fluid (PF) of infertile women with minimal and mild endometriosis. MATERIALS AND METHODS: 19 women were studied, including 9 infertile women with minimal or mild endometriosis and 10 patients with tubal occlusion (the reference group). Lipid peroxides (malonyldialdehyde and 4-hydroxynonenal), TNF-alpha and IFN-gamma concentrations were measured in the PF using commercially available kits. RESULTS: Concentration of IFN-gamma was detectable in PF of 7 (77.8%) women with endometriosis and in PF from 3 (30%) patients with tubal occlusion. Neither TNF-alpha or lipid peroxides PF concentration differed significantly (p < 0.05) between the groups. In the group with endometriosis we have found a positive correlation (R = 0.77, p = 0.04) between the concentrations of TNF-alpha and IFN-gamma. CONCLUSIONS: Our results suggest that oxidative stress in the PF doesn't appear to play a role in endometriosis-associated infertility.     

Antizona and antisperm antibodies in women with endometriosis and/or infertility

OBJECTIVE: To measure the levels of antigamete antibodies in serum and peritoneal fluid of women with endometriosis and/or infertility. DESIGN: Antibody activity against human sperm and porcine oocytes was analyzed in selected subgroups of women. SETTING: Clinic of reproduction. PATIENT(S): Women with endometriosis and/or infertility. INTERVENTION(S): No treatment was implemented before peritoneal fluid and blood sample collection. MAIN OUTCOME MEASURE(S): Quantitative ELISA. RESULT(S): Four groups of women (n = 98) were analyzed for the presence of antizona and antisperm antibodies: infertile with endometriosis (n = 30), idiopathic infertility (n = 28), fertile with endometriosis (n = 20), and healthy fertile controls (n = 20). Antibodies were analyzed simultaneously in serum and peritoneal fluid. No statistically significant differences in antibody levels were detected in serum samples among the analyzed groups. The median values for antizona and antisperm antibodies in peritoneal fluid were significantly higher in women with idiopathic infertility than in the control group. In women with unexplained infertility, a high degree of correlation (Spearman) was found between the presence of antizona antibodies in peritoneal fluid and serum (r = 0.579). A positive predictive value of 80% was calculated for the presence of antizona antibodies (>5 ng/oocyte) in the peritoneal fluid of patients with infertility. CONCLUSION(S): Antizona antibodies locally produced in the peritoneal fluid have diagnostic value for infertility status; however, they cannot be treated as a marker or prognostic factor for minimal endometriosis and/or its treatment.     

Dexamethasone or interleukin-10 blocks interleukin-1beta-induced uterine contractions in pregnant rhesus monkeys

OBJECTIVE: The purpose of this study was to determine whether treatment with the immune modulators dexamethasone or interleukin-10 prevents interleukin-1beta-induced uterine contractions in a nonhuman primate model. STUDY DESIGN: Thirteen chronically instrumented rhesus monkeys at 135 +/- 1 days of gestation (term, 167 days) received one of three interventions: (1) intra-amniotic interleukin-1beta (10 microg) infusion with maternal dexamethasone (1 mg/kg) intravenously every 6 hours for 1 day before interleukin-1beta and for 2 days thereafter (n = 4), (2) intra-amniotic interleukin-1beta infusion with maternal interleukin-10 (25 microg/kg) given intravenously and 100 microg interleukin-10 given intra-amniotically before the interleukin-1beta and continued every 8 hours for 3 days (n = 5), and (3) intra-amniotic interleukin-1beta administered alone (n = 5). Uterine activity was monitored continuously and quantified as the hourly contraction area (millimeters of mercury times seconds per hour) in all groups until delivery. Amniotic fluid was sampled for leukocyte counts and assayed for prostaglandins E(2) and F(2)alpha, cytokines interleukin-1beta, interleukin-6, interleukin-8, tumor necrosis factor-alpha, interleukin-10, and interleukin-1 receptor antagonist by specific assays. Maternal and fetal blood were assayed for cortisol, dehydroepiandrosterone sulfate, and estradiol. RESULTS: Interleukin-1beta infusion in the absence of immune modulators resulted in an increase in uterine activity and amniotic fluid proinflammatory cytokines, prostaglandins, and leukocytes. Dexamethasone and interleukin-10 treatment significantly reduced interleukin-1beta-induced uterine contractility (P <.05) and amniotic fluid prostaglandins (P <.05) but not interleukin-8 or interleukin-1 receptor antagonist. Amniotic fluid interleukin-6 and maternal and fetal cortisol, dehydroepiandrosterone sulfate, and estradiol concentrations were reduced by dexamethasone (P <.05), whereas tumor necrosis factor-alpha levels and leukocyte counts were attenuated by interleukin-10 treatment (P <.05). An inverse relationship was noted between amniotic fluid interleukin-10 concentrations and interleukin-1beta-induced uterine activity (r = -0.74, P <.05). CONCLUSION: Dexamethasone and interleukin-10 exert similar inhibitory effects on interleukin-1beta-induced uterine activity, which appears to be mediated by a decrease in prostaglandin production. Reduced estrogen biosynthesis or suppression of tumor necrosis factor-alpha and leukocyte migration may contribute to the tocolytic actions of dexamethasone and interleukin-10, respectively. Dexamethasone and interleukin-10 are likely to be useful adjuncts in the treatment of preterm labor that is associated with inflammation or infection.