Association of leptin with inflammatory cytokines and lymphocyte subpopulations in peritoneal fluid of patients with endometriosis

INTRODUCTION: Endometriosis is a common, complex and chronic disease related to ectopic implantation and growth of endometrial tissue that may manifest by pelvic inflammatory reactions, chronic pelvic pain and subfertility. Endometriosis may be associated with increased peritoneal fluid leptin levels. Leptin is known to exert immunomodulatory effects; however, an association between leptin and inflammatory reactions in endometriosis has not been documented. Therefore, the aim of this study was to investigate a relationship between leptin concentrations in peritoneal fluid and the levels of peritoneal fluid inflammatory cytokines and mononuclear leukocyte subpopulations. MATERIALS AND METHODS: Peritoneal fluid was aspirated by laparoscopy from 46 women in whom endometriosis had been confirmed by clinical and histopathological examinations and from 10 control women qualified for ART in whom pelvic pathology has been excluded. Concentrations of leptin and inflammatory cytokines (IL-1beta, IL-6, IFN-gamma and TNF) in peritoneal fluid were evaluated by specific ELISAs. Percentage of peritoneal leukocyte subpopulations (CD3+, CD4+, CD8+ and CD14+) was analyzed by FACS using specific monoclonal antibodies. RESULTS: Leptin concentrations in peritoneal fluid correlated negatively with concentrations of IL-1beta and IFN-gamma (r(s)=-0.38, p=0.01 and r(s)=-0.31, p=0.03, respectively) and correlated positively with the percentage of CD3+ pan-T cells (r(s)=0.69, p=0.009) and CD4+ T helper cells (r(s)=0.74, p=0.036). CONCLUSIONS: Increased leptin levels in peritoneal fluid from endometriosis patients may affect local inflammatory/immune reactions, especially infiltration of CD4+ T helper cells. Thus, leptin may play an important role in the immunopathogenesis of endometriosis.     

Correlations between concentrations of interleukin-12 and interleukin-13 and lymphocyte subsets in the follicular fluid of women with and without polycystic ovary syndrome

OBJECTIVE: To investigate a possible correlation between interleukin-12 (IL-12) and IL-13 levels and lymphocyte subsets in the preovulatory follicles of patients with and without polycystic ovarian syndrome (PCOS). DESIGN: Controlled clinical study. SETTING: University hospital. PATIENT(S): Seventy-eight infertile women undergoing IVF-embryo transfer. INTERVENTION(S): The subjects underwent blood sampling, ovum retrieval, and embryo transfer. MAIN OUTCOME MEASURES: Follicular fluid levels of T, androstenedione (A); IL-12, IL-13, activated T cells, T helper, and T-suppressor lymphocytes. RESULT(S): The level of IL-12 detected in follicular fluid (FF) was significantly lower in patients with PCOS than in normally ovulating women (mean: 1.47 +/- 0.3 pg/mL vs. 2.25 +/- 0.7 pg/mL, respectively); in contrast, FF IL-13 concentrations were significantly higher in the patients with PCOS than in the normally ovulating women (mean: 32.5 +/- 3.7 pg/mL vs. 19.6 +/- 2.5 pg/mL, respectively), as was the total number of activated T lymphocytes (11.5% +/- 1.5% vs. 4.8% +/- 0.4%). A significant correlation was observed between FF activated T-cell concentrations and FF IL-12, IL-13, T, and A levels. No significant differences were observed when these data were compared with embryological parameters. CONCLUSION(S): The present study shows significant differences in the correlation between FF IL-12 and IL-13 levels and T lymphocyte numbers in the subset of patients with PCOS as compared to normally ovulating women.     

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 )     

Effect of ovarian involvement on peritoneal fluid cytokine concentrations in endometriosis patients

Peritoneal fluid cytokines are important for initiation and progression of endometriosis. The objective of this study was to compare a group of five cytokines (interleukins IL-1 beta, IL-6, IL-8, IL-13 and tumour necrosis factor alpha; TNFalpha) in peritoneal fluid of endometriosis patients with ovarian involvement (Group I, n = 17) to those in patients without ovarian involvement (Group II, n = 33) and to a reference group without endometriosis (Group III, n = 25). All three groups were comparable regarding age, parity and body mass index. IL-8 concentrations were significantly higher in groups I and II compared with the reference group (P = 0.01 and 0.02, respectively). Similarly, TNFalpha concentrations were significantly higher in groups I and II compared with the reference group (P < 0.0001 and 0.0004, respectively). All other cytokines were comparable in the three groups. No significant differences were found between groups I and II with respect to the cytokines measured. In conclusion, peritoneal fluid IL-8 and TNFalpha concentrations are significantly higher in endometriosis. Ovarian involvement does not alter the pattern of cytokines. It appears that the inflammatory mediators of endometriosis are similar with and without ovarian involvement.     

Increased levels of human neutrophil peptides 1, 2, and 3 in peritoneal fluid of patients with endometriosis: association with neutrophils, T cells and IL-8

Endometriosis is a common gynaecological disorder characterized by the presence of endometrial tissue outside the uterine cavity. This disease is associated with pelvic inflammation and displays some features of autoimmune disorder. Human neutrophil peptides 1, 2, and 3 (HNP 1-3) belonging to α-defensin family play a crucial role in innate immunity against infections and may exert immunoregulatory effects. They may play a role in various inflammatory reactions; however, their role in endometriosis has not been studied. Therefore, the aim of the present study was to evaluate HNP 1-3 in the peritoneal fluid of 67 patients with endometriosis and 16 healthy control women in relation to peritoneal leukocyte subpopulations (neutrophils, T cells, and macrophages) and inflammatory cytokines (IL-6 and IL-8). HNP 1-3, IL-6 and IL-8 were evaluated in the peritoneal fluid by specific enzyme-linked immunosorbent assays (ELISA), and peritoneal leukocyte subpopulations were evaluated by flow cytometry. We found that the levels of HNP 1-3 were significantly increased in the peritoneal fluid of endometriosis patients, compared with control women, and correlated with severity of the disease. Endometriosis was also associated with increased concentrations of peritoneal neutrophils. In endometriosis the levels of HNP 1-3 strongly correlated with concentrations of neutrophils, T cells and IL-8. HNP 1-3 levels were not associated with peritoneal IL-6 or macrophages. These data suggest that HNP 1-3 and neutrophils might play a role in immunopathogenesis of endometriosis and may be worth evaluating as targets for anti-endometriosis therapy.     

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.     

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.     

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.     

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.     

盆腔子宫内膜异位症患者NK细胞表面自然细胞毒受体表达的研究

目的:探讨盆腔子宫内膜异位症患者外周血和腹腔液NK细胞表面自然细胞毒受体的表达及意义。方法:用流式细胞术直标法检测20例盆腔子宫内膜异位症患者和13例非子宫内膜异位症对照者外周血和腹腔液NK细胞表面自然细胞毒受体NKp30、NKp44和NKp46的表达。结果:(1)NKp30在腹腔液CD56+NK细胞表面表达观察组较对照组明显减少(P<0.05),在腹腔液CD16+NK细胞表面和外周血CD56+/CD16+NK细胞表面表达两组之间则无差异;NKp46在外周血和腹腔液CD56+/CD16+NK细胞表面表达观察组和对照组之间无显著差异;NKp44在外周血和腹腔液CD56+/CD16+NK细胞表面均无表达;(2)NKp30在腹腔液CD56+CD16+NK细胞上表达观察组比对照组明显减少;外周血CD56+CD16+NK细胞表面NKp30表达以及外周血和腹腔液CD56+CD16+NK细胞表面NKp46表达观察组和对照组之间则无差异;(3)NKp30和NKp46在腹腔液CD16+NK细胞表面表达较外周血显著降低(PNKp30<0.05;PNKp46<0.01),而CD56+NK细胞表面外周血和腹腔液之间的表达则无差异。结论:腹腔液NK细胞表面自然细胞毒受体NKp30在盆腔子宫内膜异位症发病过程中起作用。     

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 regulation of immunoglobulin production by B cells in patients with endometriosis

Nineteen patients with endometriosis and 26 control infertile patients were included in the study. All patients were undergoing laparoscopy as part of their infertility evaluations. The study was conducted on sterile heparinized peripheral blood and peritoneal fluid. The age range was 20 to 37 years for both groups. Mononuclear cells were isolated on Ficoll-hypaque density gradients. T cells, B cells, and T cell subsets were identified by the specific immunobead rosette technique. Mononuclear cells 1 x 10(6) were cultured in Roswell Park Memorial Institute medium and stimulated in the presence or absence of pokeweed mitogen. Immunoglobulin production was measured by an enzyme-linked immunosorbent assay. Increased amounts of immunoglobulin (Ig) IgG and IgA were demonstrated in the peritoneal cell cultures (P less than 0.05), whereas peripheral blood cell cultures showed only an increase in IgG in patients with endometriosis (P less than 0.05). There was an increase in the number of T cells, B cells, and the ratio of CD4/CD8 lymphocytes in endometriosis compared with control patients (P less than 0.005) in both peritoneal fluid and peripheral blood. This study suggests that immunoglobulin production by the "activated" B cells may be regulated by the increased presence of T cells, specifically the helper cells (CD4) in endometriosis.     

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.     

Is endometriosis associated with systemic subclinical inflammation?

Endometriosis is a pelvic inflammatory process with altered function of immune-related cells and increased number of activated macrophages in the peritoneal environment that secrete various local products, such as growth factors and cytokines. The elevation of cytokines and other factors in the peritoneal fluid is accompanied by the elevation of similar factors, such as CRP, SAA, TNF-alpha, MCP-1, IL-6, IL-8 and CCR1, in the peripheral blood of patients with endometriosis. CD44+ and CD14+ monocytes are significantly increased, while CD3+ T lymphocytes and CD20+ B lymphocytes show modest, but significant decrease in peripheral blood of women with endometriosis. This indicates that endometriosis could be viewed as a local disease with systemic subclinical manifestations. This review provides an overview of data on the changes of various factors in peripheral blood and their potential use as diagnostic tools in patients with endometriosis.     

T helper (Th)1, Th2, and Th17 interleukin pathways in infertile patients with minimal/mild endometriosis

In the present study, interleukin (IL)-10, IL-12, IL-17, and IL-23 levels were measured in serum and peritoneal fluid of women with minimal or mild endometriosis and compared with levels in controls without endometriosis. Higher IL-23 levels were encountered in the peritoneal fluid of women with endometriosis, suggesting a possible role of this cytokine in these women's infertility.     

The evaluation of IL-12 levels in peritoneal fluid and serum of women with endometriosis

We studied levels of IL-12 in peritoneal fluid and serum in patients with minimal, advanced and recurrent endometriosis compared to women without endometriotic lesions in pelvis minor. The aim of the study was to determine whether level of IL-12 detected in peritoneal fluid or serum changes with grading of severity of endometriosis. To assess IL-12 levels immunosorbent ELISA was used. There were no statistically significant differences in IL-12 levels in peritoneal fluid nor in serum in any of studied groups. There was higher concentration (without statistical significance) of IL-12 in peritoneal fluid of healthy women compared to women with endometriosis.     

子宫内膜异位症患者腹腔液白细胞介素17水平的变化及其意义

目的探讨白细胞介素17(IL17)与子宫内膜异位症(内异症)发病的关系。方法应用酶联免疫吸附(ELISA)法检测36例不同期别内异症患者(内异症组)和26例非内异症患者(对照组)腹腔液中的IL17水平。结果内异症组和对照组腹腔液IL17水平分别为(5.7±1.9)ng/L和(5.3±1.4)ng/L,两组比较,差异无统计学意义(P>0.05)。按1985年美国生育学会内异症分期标准(rAFS)进行分期,Ⅰ～Ⅱ期内异症患者(16例)腹腔液IL17水平为(6.4±1.7)ng/L,Ⅲ～Ⅳ期内异症患者(20例)为(5.1±1.8)ng/L,两者比较,差异有统计学意义(P<0.05)。卵泡期和黄体期腹腔液IL17水平在两组间比较,差异均无统计学意义(P>0.05)。内异症不孕患者腹腔液IL17水平为(6.4±1.8)ng/L,内异症未合并不孕患者为(5.1±1.8)ng/L,两者比较,差异有统计学意义(P<0.05)。结论IL17水平变化可能与早期内异症及内异症不孕的发病有关。     

Immune rosettes of T and B lymphocytes in infertile women with endometriosis

We examined the cell-mediated immune response in women with pelvic endometriosis by quantitating their T and B lymphocytes. The study was conducted on heparinized peripheral blood and peritoneal fluid. The results were compared with those in a control group of women without evidence of endometriosis. Each patient underwent laparoscopy as part of her infertility evaluation. The ability of T cells to form rosettes with sheep erythrocytes was used to estimate the percentage of total and active T cells. B lymphocytes were quantitated by erythrocyte antibody complement binding capacity. In addition, T and B lymphocytes were assayed with the Immunobead technique using specific monoclonal antibodies. The helper T cell (T4) and suppressor T cell (T8) subsets of lymphocytes were evaluated with specific monoclonal antibodies coupled to microbeads. The results demonstrated an increased number of T and B cells in peritoneal fluid and peripheral blood from patients with endometriosis as compared with controls. Furthermore, the ratio T4:T8 was significantly increased in patients with endometriosis. These results suggest a cell-mediated immune response in the presence of endometriosis.     

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.     

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.