人白介素13在盆腔子宫内膜异位症患者血清和腹腔液中的表达及意义
|
摘要
研究背景与目的：
子宫内膜异位症(Endometriosis, EMs)是生育期年龄妇女常见的妇科疾病之一总发病率10%-15%,在不孕症或慢性盆腔痛的妇女中发病率均高达30%以上。其发病机理尚未完全被阐明,尽管Sampson提出的种植学说已经得到广泛认同,然而研究发现,子宫内膜碎片逆流至盆腔只是诱因,其异位黏附、种植、生长才是EMs发病的关键。随着免疫学的观点日益深入,免疫因素特别是细胞因子在EMs发病机制中的作用越来越受到重视。
细胞因子(cytokine)是由细胞合成与分泌的一类具有生物活性的小分子多肽的统称,是免疫系统的一个组成部分,广泛参与全身免疫反应。目前认为,盆腔微环境的免疫失衡是子宫内膜异位症发病机制中的一个关键因素,而腹腔液中异常表达的细胞因子为逆流至盆腔的子宫内膜提供一个良好的种植、生长环境。
白介素13 (interleukin-13, IL-13)是1994年被首次发现,具有广泛而复杂的免疫调节和抗炎作用。尽管对于IL-13的生物学特征有深入地研究,但是它在子宫内膜异位症发病机制中的作用尚不清楚。
本研究通过检测及探讨子宫内膜异位症患者血清及腹腔液中IL-13水平的变化,初步推测其在内异症发病中的作用。
研究对象与方法：
1、研究对象：子宫内膜异位症组(研究组,简称内异组,下同)取自2009年12月至2010年4月在我院妇科住院病人并行腹腔镜手术,术中腹腔镜下和术后病理诊断为EMS的患者32例。对照组取自同期因子宫肌瘤或卵巢良性肿瘤住我院妇科进行腹腔镜手术治疗的患者20例。
2、方法：采用酶联免疫吸附试验(ELISA),检测内异症组32例患者和对照组20例非内异症患者腹腔液及血清中IL-13的水平,比较两组之间的差异；比较两组在月经周期中的变化；分析内异组和对照组中血清IL-13水平和腹腔液IL-13水平之间的相关性；并将内异组血清及腹水IL-13水平分别与内异症R-AFS评分进行相关性分析。应用SPSS 17.0软件包进行统计学分析。
结果：
1、内异症组血清IL-13水平(6.95±2.74 pg/ml)明显低于对照组(12.87±9.70pg/ml) (p<0.005);内异组腹腔液IL-13水平(3.26±1.81 pg/ml)明显低于对照组(8.49±6.65 pg/ml) (p<0.001).
2、根据期别将内异组分为内异轻度组(Ⅰ、Ⅱ期)和内异重度组(Ⅲ、Ⅳ期),血清IL-13水平内异轻度组(7.85±2.09 pg／ml)与对照组(12.87±9.70pg/ml)及内异轻度组(7.85±2.09 pg/ml)与重度组为(6.34±3.00 pg/ml)均无显著差异(P>0.05),内异重度组(6.34±3.00 pg／ml)明显低于对照组(12.87±9.70 pg／ml)(P<0.05)；腹腔液IL-13水平内异重度组(2.43±1.43pg/ml)明显低于轻度组(4.48±1.63 pg/ml) (P<0.005),后者又显著低于对照组(8.49±6.65pg/ml) (P<0.05).
3、对照组血清IL-13水平和腹腔液IL-13水平呈正相关(r=0.875,P<0.01)；内异组腹腔液IL-13表达水平与其R-AFS评分呈负相关(r=-0.52,P<0.05)。
4、月经周期中内异组、对照组血清及腹腔液IL-13表达无显著差异(p>0.05)。
结论：
1、内异症患者腹腔液中IL-13的水平显著降低,且与疾病的严重程度呈负相关,推测IL-13在内异症的发病中可能起一定的作用。
2、月经周期中内异组、对照组血清及腹腔液IL-13表达无显著差异,推测血清及腹腔液中IL-13水平可能不受月经周期的影响。
Background and Objective:
Endometriosis(EMs) is a common gynecologic disease, with the incidence 10～15%of women in general population. The attack rate is as high as 30%in women with infertility or chronic pelvic plain. The pathogenesis of endometriosis is not distinct. Retrograde menstruation is a widely accepted mechanism that could explain the presence of endometrial cells in ectopic sites. However, it does not account for the fact that these misplaced cells survive in women with the disease and not in healthy ones. An immunological etiology has been conjectured, as demonstrated by increased concentrations of the cytokine secreted by activated macrophages, T and B cells.
Cytokine, a bioactive polypeptide with low molecular weight, is synthesized and secreted by some kind of cells. Immunologic dissonance in pelvic microenvironment plays an important role in development of endometriosis. Studies have reported abnormal levels of cytokines in the peritoneal fluid of endometriosis, thus implicating these factors in the genesis and progression of the disease.
Interleukin-13 was firstly discovered in 1994, which plays a role as both immunoregulator and anti-inflammation factor. Although IL-13 stands as one of the most investigated disorders of some disease else, our current understanding of its role in endometriosis remains elusive.
The objective of the present study is to detect the variation of IL-13 level in serum and peritoneal fluid of endometriosis, and to investigate the role of IL-13 in the pathogenesis of EMs.
Materials and methods:
Expression of IL-13 was detected the IL-13 level in peritoneal fluid and serum of 32 cases with EMs (Study group, EMs group) and counterpart of 20 cases without Ems (control group) by enzyme-linked immunosorbent assay (ELISA), the variation of IL-13 level in menstrual cycle is compared between study group and control group, and the correlation is analysed not only between IL-13 level and the Revisal-American Fertility Score (R-AFS) but also between IL-13 level in serum and in peritoneal fluid. All study subjects were recruited from Women's Hospital, College of Medicine, Zhejiang University, from December.2009 to April.2010.
Results:
1、IL-13 level in serum with Ems (6.95±2.74 pg/ml) was significantly lower than that in control group (12.87±9.70 pg/ml)(p<0.05), as same as that in peritoneal fluid of between EMs group (3.26±1.81 pg/ml) and control group (8.49±6.65 pg/ml)(p<0.001).
2、EMs group has been divided into mild(stageⅠandⅡ) and severe group(stageⅢandⅣ) according to the stage of EMs. IL-13 level in serum has not difference not only between control group(12.87±9.70 pg/ml) and mild group(7.85±2.09 pg/ml) but also between mild group(7.85±2.09 pg/ml) and severe group(6.34±3.00 pg/ml)(p>0.05). however, IL-13 level of severe group(6.34±3.00 pg/ml) was significant lower than that of control group(12.87±9.70 pg/ml) (p<0.05). IL-13 level in peritoneal fluid of severe group(2.43±1.43pg/ml) was significant lower than that in mild group(4.48±1.63 pg/ml)(P<0.005), and IL-13 level in mild group(4.48±1.63 pg/ml) was significant lower than that in control group(8.49±6.65pg/ml) (P<0.05).
3、IL-13 level in peritoneal fluid of EMs group has the negative correlation with R-AFS, and of control group, IL-13 level in serum has the positive correlation with that in peritoneal fluid.
4、IL-13 level has no difference in menstrual cycle.
Conclusions:
1、IL-13 level which is low in peritoneal fluid has negative correlation with the severity of EMS, may play an important role in the pathogenesis of EMs.
2、It has been surmised that there may be no cycle-specific differences in IL-13 level of both serum and peritoneal fluid in each group.
子宫内膜异位症(Endometriosis, EMs)是生育期年龄妇女常见的妇科疾病之一总发病率10%-15%,在不孕症或慢性盆腔痛的妇女中发病率均高达30%以上。其发病机理尚未完全被阐明,尽管Sampson提出的种植学说已经得到广泛认同,然而研究发现,子宫内膜碎片逆流至盆腔只是诱因,其异位黏附、种植、生长才是EMs发病的关键。随着免疫学的观点日益深入,免疫因素特别是细胞因子在EMs发病机制中的作用越来越受到重视。
细胞因子(cytokine)是由细胞合成与分泌的一类具有生物活性的小分子多肽的统称,是免疫系统的一个组成部分,广泛参与全身免疫反应。目前认为,盆腔微环境的免疫失衡是子宫内膜异位症发病机制中的一个关键因素,而腹腔液中异常表达的细胞因子为逆流至盆腔的子宫内膜提供一个良好的种植、生长环境。
白介素13 (interleukin-13, IL-13)是1994年被首次发现,具有广泛而复杂的免疫调节和抗炎作用。尽管对于IL-13的生物学特征有深入地研究,但是它在子宫内膜异位症发病机制中的作用尚不清楚。
本研究通过检测及探讨子宫内膜异位症患者血清及腹腔液中IL-13水平的变化,初步推测其在内异症发病中的作用。
研究对象与方法：
1、研究对象：子宫内膜异位症组(研究组,简称内异组,下同)取自2009年12月至2010年4月在我院妇科住院病人并行腹腔镜手术,术中腹腔镜下和术后病理诊断为EMS的患者32例。对照组取自同期因子宫肌瘤或卵巢良性肿瘤住我院妇科进行腹腔镜手术治疗的患者20例。
2、方法：采用酶联免疫吸附试验(ELISA),检测内异症组32例患者和对照组20例非内异症患者腹腔液及血清中IL-13的水平,比较两组之间的差异；比较两组在月经周期中的变化；分析内异组和对照组中血清IL-13水平和腹腔液IL-13水平之间的相关性；并将内异组血清及腹水IL-13水平分别与内异症R-AFS评分进行相关性分析。应用SPSS 17.0软件包进行统计学分析。
结果：
1、内异症组血清IL-13水平(6.95±2.74 pg/ml)明显低于对照组(12.87±9.70pg/ml) (p<0.005);内异组腹腔液IL-13水平(3.26±1.81 pg/ml)明显低于对照组(8.49±6.65 pg/ml) (p<0.001).
2、根据期别将内异组分为内异轻度组(Ⅰ、Ⅱ期)和内异重度组(Ⅲ、Ⅳ期),血清IL-13水平内异轻度组(7.85±2.09 pg／ml)与对照组(12.87±9.70pg/ml)及内异轻度组(7.85±2.09 pg/ml)与重度组为(6.34±3.00 pg/ml)均无显著差异(P>0.05),内异重度组(6.34±3.00 pg／ml)明显低于对照组(12.87±9.70 pg／ml)(P<0.05)；腹腔液IL-13水平内异重度组(2.43±1.43pg/ml)明显低于轻度组(4.48±1.63 pg/ml) (P<0.005),后者又显著低于对照组(8.49±6.65pg/ml) (P<0.05).
3、对照组血清IL-13水平和腹腔液IL-13水平呈正相关(r=0.875,P<0.01)；内异组腹腔液IL-13表达水平与其R-AFS评分呈负相关(r=-0.52,P<0.05)。
4、月经周期中内异组、对照组血清及腹腔液IL-13表达无显著差异(p>0.05)。
结论：
1、内异症患者腹腔液中IL-13的水平显著降低,且与疾病的严重程度呈负相关,推测IL-13在内异症的发病中可能起一定的作用。
2、月经周期中内异组、对照组血清及腹腔液IL-13表达无显著差异,推测血清及腹腔液中IL-13水平可能不受月经周期的影响。
Background and Objective:
Endometriosis(EMs) is a common gynecologic disease, with the incidence 10～15%of women in general population. The attack rate is as high as 30%in women with infertility or chronic pelvic plain. The pathogenesis of endometriosis is not distinct. Retrograde menstruation is a widely accepted mechanism that could explain the presence of endometrial cells in ectopic sites. However, it does not account for the fact that these misplaced cells survive in women with the disease and not in healthy ones. An immunological etiology has been conjectured, as demonstrated by increased concentrations of the cytokine secreted by activated macrophages, T and B cells.
Cytokine, a bioactive polypeptide with low molecular weight, is synthesized and secreted by some kind of cells. Immunologic dissonance in pelvic microenvironment plays an important role in development of endometriosis. Studies have reported abnormal levels of cytokines in the peritoneal fluid of endometriosis, thus implicating these factors in the genesis and progression of the disease.
Interleukin-13 was firstly discovered in 1994, which plays a role as both immunoregulator and anti-inflammation factor. Although IL-13 stands as one of the most investigated disorders of some disease else, our current understanding of its role in endometriosis remains elusive.
The objective of the present study is to detect the variation of IL-13 level in serum and peritoneal fluid of endometriosis, and to investigate the role of IL-13 in the pathogenesis of EMs.
Materials and methods:
Expression of IL-13 was detected the IL-13 level in peritoneal fluid and serum of 32 cases with EMs (Study group, EMs group) and counterpart of 20 cases without Ems (control group) by enzyme-linked immunosorbent assay (ELISA), the variation of IL-13 level in menstrual cycle is compared between study group and control group, and the correlation is analysed not only between IL-13 level and the Revisal-American Fertility Score (R-AFS) but also between IL-13 level in serum and in peritoneal fluid. All study subjects were recruited from Women's Hospital, College of Medicine, Zhejiang University, from December.2009 to April.2010.
Results:
1、IL-13 level in serum with Ems (6.95±2.74 pg/ml) was significantly lower than that in control group (12.87±9.70 pg/ml)(p<0.05), as same as that in peritoneal fluid of between EMs group (3.26±1.81 pg/ml) and control group (8.49±6.65 pg/ml)(p<0.001).
2、EMs group has been divided into mild(stageⅠandⅡ) and severe group(stageⅢandⅣ) according to the stage of EMs. IL-13 level in serum has not difference not only between control group(12.87±9.70 pg/ml) and mild group(7.85±2.09 pg/ml) but also between mild group(7.85±2.09 pg/ml) and severe group(6.34±3.00 pg/ml)(p>0.05). however, IL-13 level of severe group(6.34±3.00 pg/ml) was significant lower than that of control group(12.87±9.70 pg/ml) (p<0.05). IL-13 level in peritoneal fluid of severe group(2.43±1.43pg/ml) was significant lower than that in mild group(4.48±1.63 pg/ml)(P<0.005), and IL-13 level in mild group(4.48±1.63 pg/ml) was significant lower than that in control group(8.49±6.65pg/ml) (P<0.05).
3、IL-13 level in peritoneal fluid of EMs group has the negative correlation with R-AFS, and of control group, IL-13 level in serum has the positive correlation with that in peritoneal fluid.
4、IL-13 level has no difference in menstrual cycle.
Conclusions:
1、IL-13 level which is low in peritoneal fluid has negative correlation with the severity of EMS, may play an important role in the pathogenesis of EMs.
2、It has been surmised that there may be no cycle-specific differences in IL-13 level of both serum and peritoneal fluid in each group.
引文
[1]Giudice L, Kao L. Endometriosis[J]. Lancet,2004,364(94):1789-1799
[2]Sten E W, Jacobsen, Cecilie Okkcenaug, et al. Interleukin 13:novel role in direct regulation proliferation and differentiation of primitive hematopcietic progenitor cells. J Exp Med,1994;180:75
[3]Chomarat P, Bannchereau J:Interleukin-4 and interleukin-13:their similarities and discrepancies. Int Rev Immunol 1998; 17:1-52
[4]Brombacher F:The role of interleukin-13 in infectious diseases and allergy. Bioessays 2000;22:646-656
[5]Opal SM, DePalo VA:Anti-inflammatory cytokines. Chest 2000; 117:1162-1172.
[6]Di Santo E, Meazza C, et al. IL-13 inhibits TNF-α production but potentiates that of IL-6 in vivo and ex vivo in mice. J Immunol 1997; 159:379-382
[7]Hart PH, Bonder CS, et al. Differential responses of human monocytes and macrophages to IL-4 and IL-13. J Leukoc Biol 1999;66:575-578
[8]Muchamuel T, Menon S, et al. IL-13 protects mice from lipopolysaccharide-induced lethal endotoxemia:correlation with down-modulation of TNF-a, IFN-c, and IL-12 production. J Immunol 1997; 158:2898-2903.
[9]Mijatovic T, Kruys V, et al. Interleukin-4 and-13 inhibit tumor necrosis factor-α mRNA translational activation in lipopolysaccharide-induced mouse macrophages. J Biol Chem 1997;272:14,394-14,398
[10]D'Hooghe TM, Debrock S, Hill JA, et al. Endometriosis and subfertility:is the relationship resolved? [J]. Semin Reprod Med,2003,21(2):243-254.
[11]Agic A, Xu H, Finas D, et al. Is endometriosis associated with systemic subclinical inflammation? [J]. Gynecol Obstet Invest,2006,62(3):139-147.
[12]Vinatier D, Dufour P. et al. Immunological aspects of endometriosis. Hum Reprod update,1996,2(3):381-384
[13]Kats R, Collette T, Metz CN, et al. Marked elevation of macrophage migration inhibitory factor in the peritoneal fluid of women with endometriosis. Fertil Steril,2002,78(1):69-76
[14]Donald P, BraunD, JianchiD, etal. Peritoneal fluid mediated enhancement of eutopic and ectopic endometrial cell proliferation is dependent on tumor necrosis factor-alpha in women with endometriosis. Fertility and Sterility,2002,78(4): 727-732
[15]Pizzo A, Salmeri FM, Ardita FV, et al. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis[J]. Gynecol Obstet Invest,2002, 54(2):82-87.
[16]Yamanehi N, Hamda T, Tnaiugchi F, et la. Tumorv necrosis factor-alpha induced the release of interleukin-6 from endometriotic storma lcells by the nuclear factor-kappaB and mitogen-activated protein kinsae pathways. Fertil Steril, 2004,82[Supp]31:1023-102
[17]Simon C, Frances A, Piquette GN, el Danasouri I, ZurawskiG, Dang W. Embryonic implantation in mice is blocked by interleukin-1 receptor antagonist. Endocrinology 1994;134:521-528.
[18]KhamKN, MasazakiH, FujishitaA. Association of interleukin-6 and estradiol with hepatocye growth factor in peritoneal fluid of women with endometriosis. Acta Obstet Gynecol Scand,2002,81(8):764-771
[19]TsudoT, HaradaT, et al. Alteredgene expression and secretion of interleukin — 6 instromal cells derived from endometriotic tissue. Fertil Steril,2000;73:205-211
[20]Selam B, Kayisli UA, et al. Regulation of Fas ligand expression by IL-8 in human ndometrium [J]. J Clin Endocrinol Metab,2002,87(8):3921-3927.
[21]Kitanwaki J, Oayashi H, Ohta M. Genetic contribution of the IL-10 promotor polymorphism in endometriosis suspetibility. Am J Reprod Immunol,2002, 47(1):12-18
[22]Gineko P. The elevation of IL-12 levels in peritoneal fluid and serum of women with endometriosis. Hum Reprod,2001,72(5):408-417
[23]Matarese G, De Placido G, et al. Pathogenesis of endometriosis:natural immunity dysfunction or autoimmune disease[[J]. Trends Mol Med,2003,9(5):223-228.
[24]Vigano P, Somigllliana E, et al. Endometrial release of soluble intercellular adhesion molecule-1 and endometriosis:relationship to the extent of the disease. Obstet Gynecol,2000,95(1):115
[25]McLaren J, Dealtry G, et al. Decreased levels of the potent regulator of monocyte/macrophage activation,interleukin-13, in the peritoneal fluid of patients with endometriosis. Human Reproduction 1997,12 (6):1307-1310
[26]Zurawski G, Devries JE. IL-13, and IL-4-like cytokine that act on monocytes and Bcell, but not on T cell. Immune Today,1994; 15:19
[27]Mckenzie ANJ, Li X, et al. Structural comparison and chromosomal localization of the human and mouse IL-13 gense [J]. J Immunol,1993,150:5436-5444.
[28]Hart PH, Bonder CS, et al. Differential responses of human monocyte and macrophages to IL-4 and IL-13 [J]. J Leukoc Biol,1999,66:575-578
[29]Chomarat P, Bannchereau J. Interleukin-4 and inter-leukin-13:their similarities and discrepancies. Int Rev Immunol 1998;17:1-52.
[30]Waldmann TA,Tagaya Y. The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens. Annu Rev Immunol 1999; 17:19-49.
[31]Gauchat JF, Schlagenhauf E, et al. A novel 4-kb interleukin-13 receptor alpha mRNA expressed in human B,T and endothelial cells encoding an laternate type-II interleukin-4/interleukin-13 receptor. Eur j Immune.1997;27:971
[32]Malefyt DR, Figdor GC, et al. Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. J Immunology, 1993;151:6370
[33]Punnonen J, Aversa G, et al. Interleukin-13 induces interleukin-4-independent IgG4 and IgE synthesis and CD23 expression by human B cell. Immunology, 1993;90:3730
[34]Brombacher F. The role of interleukin-13 in infectious diseases and allergy. Bioessays 2000;22:646-656.
[35]Di Santo E, Meazza C,et al. IL-13 inhibits TNF-a production but potentiates that of IL-6 in vivo and ex vivo in mice. J Immunol 1997;159:379-382.
[36]Hart PH, Bonder CS, et al. Differential responses of human monocytes and macrophages to IL-4 and IL-13. J Leukoc Biol 1999;66:575-578.
[37]Muchamuel T, Menon S, et al. IL-13 protects mice from lipopolysaccharide-induced lethal endotoxemia:correlation with down-modulation of TNF-a, IFN-y, and IL-12 production. J Immunol 1997;158:2898-2903.
[38]Mijatovic T, Kruys V, et al. nterleukin-4 and-13 inhibit tumor necrosis factor-a mRNA translational activation in lipopolysaccharide-induced mouse macrophages. J Biol Chem 1997;272:14,394-14,398.
[39]Bulfone-Paus S, Bulanova E, et al. Death deflected:IL-15 inhibits TNF-a-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Ra chain. FASEB J 1999;13:1575-1585.
[40]Fehniger TA, Caligiuri MA. Interleukin 15:biology andrelevance to human disease.Blood 2001;97:14-32.
[41]Marks-Konczalik J, Dubois S, et al. IL-2-in-duced activation-induced cell death is inhibited in IL-15 transgenic mice. Proc Natl Acad Sci USA 2000; 97:11,445-11,450.
[42]Murata T, Taguchi J, et al. Sharing of receptor subunits and signal transduction pathway between the IL-4 and IL-13 receptor system. Int J Hematol 1999;69:13-20.
[43]Nair HM, Li S, et al. The state of maturation of monocytes into macrophages determines the effects of IL-4 and IL-13 on HIV replication. J Immunol, 1997;158:501
[44]Defrance T, Carayon P, et al. Intreleukcin-13 ks a B cell stimulating factor. J Exp Med.1994; 179:135
[45]Nilsson G, Nilsson K. Effcets of interleukin-13 on immediate-early response gene expression, phenotype and differentiation of human mast cells, comparison with IL-4. EurJImmunem,1995;25:870
[46]李大金,朱关珍,等。子宫内膜异位症的免疫功能。中国免疫学杂志,1995,11(增刊)：87-88
[47]Dmoski WP, Gebel HM, et al. The role of cell-mediated immunity in pathogenesis of endometriosis. Acta Obstet Gynecol scand,1994,159:7
[48]Ho HN, Chao KH, et al. Peritoneal natural Killer cytotoxity and CD+3CD+25 lymphocyte subpopulation are decreased in women with stage Ⅲ～Ⅳ endometriosis. HumReprod,1995,10(10):2671
[1]Pizzo A, Salmeri FM, Ardita FV, et al. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis[J]. Gynecol Obstet Invest,2002, 54(2):82-87.
[2]KhamKN, MasazakiH, FujishitaA. Association of interleukin-6 and estradiol with hepatocye growth factor in peritoneal fluid of women with endometriosis. Acta Obstet Gynecol Scand,2002,81(8):764-771
[3]Iwabe T, Harada T, Sakamoto Y, et al. Gonadotropin-releasing hormone agonist treatment reduced serum interleukin-6 concentrations in patients'with ovarian endometrismas. Fertility and Sterility,2003,80(2):300-304
[4]Rapkin A, Morgan M, Bolpane C. Peritoneal fluid interleukin-6 in women with chronic pelvic pain Fertility and Sterility,2000.74(2):325-328
[5]Bedaiwy A, Falcone T. Sharma RK. Prediction of endometriosis with serum and peritoneal fluid markers:a prospective controlled trial. Hum Reprod,2002, 17(2):426-431
[6]Mulayim N, Savlu A, Guzeloglu K O, et al. Regulation of endometrial stromal cell matrix metalloproteinase activity and invasineness by interleukin-18[J]. Fertil Steril,2004,81(suppll):904-911
[7]Selam B, Kayisli U A, Garcia V J A, et.al. Regulation of fas ligand expression by IL-18 in human endometrium[J]. J Clin Endocrinol Metab,2002,87(8): 3921-3927
[8]Selam B, Kayisli UA, Garcia-Velasco JA, et al. Regulation of Fas ligand expression by IL-8 in human ndometrium [J]. J Clin Endocrinol Metab,2002, 87(8):3921-3927.
[9]Kitanwaki J, Oayashi H, Ohta M. Genetic contribution of the IL-10 promotor polymorphism in endometriosis suspetibility. Am J Reprod Immunol,2002, 47(1):12-18
[10]Yamanehi N, Hamda T, Tnaiugchi F, et la. Tumorv necrosis factor-alpha induced the release of interleukin-6 from endometriotic storma lcells by the nuclear factor-kappaB and mitogen-activated protein kinsae pathways. Fertil Steril, 2004,82[Supp]31:1023-102
[11]BraunDP, DingJ. GogaczM, etal. Regulation of endometrial cell apoptosis by TNFa is abnormal in women with endometriosis. Fertility and Strility,2002, 77, spl:sl
[12]Donald P, BraunD, JianchiD, etal. Peritoneal fluid mediated enhancement of eutopic and ectopic endometrial cell proliferation is dependent on tumor necrosis factor-alpha in women with endometriosis. Fertility and Sterility,2002,78(4):
727—732
[13]Na YJ, Yang SH, Baek DW, et al. Effects of peritoneal fluid from endometriosis patients on the release of vascular endothelial growth factor by neutrophils and monocytes [J]. HumReprod,2006,21(7):1846-1855.
[14]邱晓红,高秀艳,李荷莲.血管内皮生长因子在子宫内膜异位症组织中的表达,吉林大学学报(医学版),2002,28(2)：147-149
[15]曹树荣,罗仪,刘永珍.血管生长因子含量与子宫内膜异位症发病的关系.湖北民族学院学报,医学版,2002,19(2)：9-12
[16]Kim JG, Suh CS, Kim SH, et all. Insulin-like growth factors IGF-I binding proteins, and IGFBP-3 protease activity in the peritoneal fluid of patients with and endometriosis [J]. Fertil Steril,2000,73(5):996
[17]Antinolo G, Fernandez R M, Noval J A, et al. Analysis of the involvement of CCR5-Delta 32 and CCR2-V64I variants in the development of endometriosis[J]. Mol HumReprod,2004,10(3):155-157
[18]Akoum Al, Kong JH, Metz C, et al. Spontaneous and stimulated secretion of monocyte chemotatic protein-1 and mancrophase migration inhibitory factor by peritoneal macrophages in women with and without endometriosis. Fertility and Sterility,2002,77(5):989～994
[19]Kats R, Collette T, Metz CN, et al. Marked elevation of macrophage migration inhibitory factor in the peritoneal fluid of women with endometriosis. Fertil Steril,2002,78(1):69-76
[20]Morin M, Bellehumeur C, Therriault MJ, et al. Elevated levels of macrophage migration inhibitory factor in the peripheral blood of women with endometriosis. Fetril Steril,2005.83(4):865-872
[21]Arici A, Matalliotakis I, Goumenou A, et al. Increased levels of interleukin-15 in the peritoneal fluid of women with endometriosis:Inverse correlation with stage and depth of invasion.Hum Reprod 2003;18:429-432.
[22]Lebovic D I, Chao V A, Taylor R N. peritoneal macrophages induce RANTES(regulated on active, normal T cell expressed and secreted) chemokine gene transcription in endometrial stroma cells[J]. J Clin Endocrine Metab,2004, 89(3):1397-1401
[23]Bedaiwy MA, Falcone T, Sharma RK, et al. Prediction of endometriosis with serum and peritoneal fluid markers:A prospective controlled trial. Hum Reprod 2002; 17:426-431.
[24]Gineko P. The elevation of IL-12 levels in peritoneal fluid and serum of women with endometriosis. Hum Reprod,2001,72(5):408-417
[25]Koga K, Osuga Y, Yoshino O, et al. Elevated interleukin-16 levels in the peritoneal fluid of women with endometriosis may be a mechanism for inflammatory reactions associated with endometriosis[J]. Fertil Steril,2005, 83(4):878-882.
[26]Lochner M,Forster I.Anti-interleukin-18 therapyin murine models of inflammatory bowel disease [J]. Pathobiology,2002,70(3):164-169.
[27]Zhang XM, Lin J, Qian Y, et al. Decreased levels of interleukin-18 in peritoneal fluid but not in serum of patients with endometriosis. Fertility and Sterility,2004(5):1229-1234
[2]Sten E W, Jacobsen, Cecilie Okkcenaug, et al. Interleukin 13:novel role in direct regulation proliferation and differentiation of primitive hematopcietic progenitor cells. J Exp Med,1994;180:75
[3]Chomarat P, Bannchereau J:Interleukin-4 and interleukin-13:their similarities and discrepancies. Int Rev Immunol 1998; 17:1-52
[4]Brombacher F:The role of interleukin-13 in infectious diseases and allergy. Bioessays 2000;22:646-656
[5]Opal SM, DePalo VA:Anti-inflammatory cytokines. Chest 2000; 117:1162-1172.
[6]Di Santo E, Meazza C, et al. IL-13 inhibits TNF-α production but potentiates that of IL-6 in vivo and ex vivo in mice. J Immunol 1997; 159:379-382
[7]Hart PH, Bonder CS, et al. Differential responses of human monocytes and macrophages to IL-4 and IL-13. J Leukoc Biol 1999;66:575-578
[8]Muchamuel T, Menon S, et al. IL-13 protects mice from lipopolysaccharide-induced lethal endotoxemia:correlation with down-modulation of TNF-a, IFN-c, and IL-12 production. J Immunol 1997; 158:2898-2903.
[9]Mijatovic T, Kruys V, et al. Interleukin-4 and-13 inhibit tumor necrosis factor-α mRNA translational activation in lipopolysaccharide-induced mouse macrophages. J Biol Chem 1997;272:14,394-14,398
[10]D'Hooghe TM, Debrock S, Hill JA, et al. Endometriosis and subfertility:is the relationship resolved? [J]. Semin Reprod Med,2003,21(2):243-254.
[11]Agic A, Xu H, Finas D, et al. Is endometriosis associated with systemic subclinical inflammation? [J]. Gynecol Obstet Invest,2006,62(3):139-147.
[12]Vinatier D, Dufour P. et al. Immunological aspects of endometriosis. Hum Reprod update,1996,2(3):381-384
[13]Kats R, Collette T, Metz CN, et al. Marked elevation of macrophage migration inhibitory factor in the peritoneal fluid of women with endometriosis. Fertil Steril,2002,78(1):69-76
[14]Donald P, BraunD, JianchiD, etal. Peritoneal fluid mediated enhancement of eutopic and ectopic endometrial cell proliferation is dependent on tumor necrosis factor-alpha in women with endometriosis. Fertility and Sterility,2002,78(4): 727-732
[15]Pizzo A, Salmeri FM, Ardita FV, et al. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis[J]. Gynecol Obstet Invest,2002, 54(2):82-87.
[16]Yamanehi N, Hamda T, Tnaiugchi F, et la. Tumorv necrosis factor-alpha induced the release of interleukin-6 from endometriotic storma lcells by the nuclear factor-kappaB and mitogen-activated protein kinsae pathways. Fertil Steril, 2004,82[Supp]31:1023-102
[17]Simon C, Frances A, Piquette GN, el Danasouri I, ZurawskiG, Dang W. Embryonic implantation in mice is blocked by interleukin-1 receptor antagonist. Endocrinology 1994;134:521-528.
[18]KhamKN, MasazakiH, FujishitaA. Association of interleukin-6 and estradiol with hepatocye growth factor in peritoneal fluid of women with endometriosis. Acta Obstet Gynecol Scand,2002,81(8):764-771
[19]TsudoT, HaradaT, et al. Alteredgene expression and secretion of interleukin — 6 instromal cells derived from endometriotic tissue. Fertil Steril,2000;73:205-211
[20]Selam B, Kayisli UA, et al. Regulation of Fas ligand expression by IL-8 in human ndometrium [J]. J Clin Endocrinol Metab,2002,87(8):3921-3927.
[21]Kitanwaki J, Oayashi H, Ohta M. Genetic contribution of the IL-10 promotor polymorphism in endometriosis suspetibility. Am J Reprod Immunol,2002, 47(1):12-18
[22]Gineko P. The elevation of IL-12 levels in peritoneal fluid and serum of women with endometriosis. Hum Reprod,2001,72(5):408-417
[23]Matarese G, De Placido G, et al. Pathogenesis of endometriosis:natural immunity dysfunction or autoimmune disease[[J]. Trends Mol Med,2003,9(5):223-228.
[24]Vigano P, Somigllliana E, et al. Endometrial release of soluble intercellular adhesion molecule-1 and endometriosis:relationship to the extent of the disease. Obstet Gynecol,2000,95(1):115
[25]McLaren J, Dealtry G, et al. Decreased levels of the potent regulator of monocyte/macrophage activation,interleukin-13, in the peritoneal fluid of patients with endometriosis. Human Reproduction 1997,12 (6):1307-1310
[26]Zurawski G, Devries JE. IL-13, and IL-4-like cytokine that act on monocytes and Bcell, but not on T cell. Immune Today,1994; 15:19
[27]Mckenzie ANJ, Li X, et al. Structural comparison and chromosomal localization of the human and mouse IL-13 gense [J]. J Immunol,1993,150:5436-5444.
[28]Hart PH, Bonder CS, et al. Differential responses of human monocyte and macrophages to IL-4 and IL-13 [J]. J Leukoc Biol,1999,66:575-578
[29]Chomarat P, Bannchereau J. Interleukin-4 and inter-leukin-13:their similarities and discrepancies. Int Rev Immunol 1998;17:1-52.
[30]Waldmann TA,Tagaya Y. The multifaceted regulation of interleukin-15 expression and the role of this cytokine in NK cell differentiation and host response to intracellular pathogens. Annu Rev Immunol 1999; 17:19-49.
[31]Gauchat JF, Schlagenhauf E, et al. A novel 4-kb interleukin-13 receptor alpha mRNA expressed in human B,T and endothelial cells encoding an laternate type-II interleukin-4/interleukin-13 receptor. Eur j Immune.1997;27:971
[32]Malefyt DR, Figdor GC, et al. Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. J Immunology, 1993;151:6370
[33]Punnonen J, Aversa G, et al. Interleukin-13 induces interleukin-4-independent IgG4 and IgE synthesis and CD23 expression by human B cell. Immunology, 1993;90:3730
[34]Brombacher F. The role of interleukin-13 in infectious diseases and allergy. Bioessays 2000;22:646-656.
[35]Di Santo E, Meazza C,et al. IL-13 inhibits TNF-a production but potentiates that of IL-6 in vivo and ex vivo in mice. J Immunol 1997;159:379-382.
[36]Hart PH, Bonder CS, et al. Differential responses of human monocytes and macrophages to IL-4 and IL-13. J Leukoc Biol 1999;66:575-578.
[37]Muchamuel T, Menon S, et al. IL-13 protects mice from lipopolysaccharide-induced lethal endotoxemia:correlation with down-modulation of TNF-a, IFN-y, and IL-12 production. J Immunol 1997;158:2898-2903.
[38]Mijatovic T, Kruys V, et al. nterleukin-4 and-13 inhibit tumor necrosis factor-a mRNA translational activation in lipopolysaccharide-induced mouse macrophages. J Biol Chem 1997;272:14,394-14,398.
[39]Bulfone-Paus S, Bulanova E, et al. Death deflected:IL-15 inhibits TNF-a-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Ra chain. FASEB J 1999;13:1575-1585.
[40]Fehniger TA, Caligiuri MA. Interleukin 15:biology andrelevance to human disease.Blood 2001;97:14-32.
[41]Marks-Konczalik J, Dubois S, et al. IL-2-in-duced activation-induced cell death is inhibited in IL-15 transgenic mice. Proc Natl Acad Sci USA 2000; 97:11,445-11,450.
[42]Murata T, Taguchi J, et al. Sharing of receptor subunits and signal transduction pathway between the IL-4 and IL-13 receptor system. Int J Hematol 1999;69:13-20.
[43]Nair HM, Li S, et al. The state of maturation of monocytes into macrophages determines the effects of IL-4 and IL-13 on HIV replication. J Immunol, 1997;158:501
[44]Defrance T, Carayon P, et al. Intreleukcin-13 ks a B cell stimulating factor. J Exp Med.1994; 179:135
[45]Nilsson G, Nilsson K. Effcets of interleukin-13 on immediate-early response gene expression, phenotype and differentiation of human mast cells, comparison with IL-4. EurJImmunem,1995;25:870
[46]李大金,朱关珍,等。子宫内膜异位症的免疫功能。中国免疫学杂志,1995,11(增刊)：87-88
[47]Dmoski WP, Gebel HM, et al. The role of cell-mediated immunity in pathogenesis of endometriosis. Acta Obstet Gynecol scand,1994,159:7
[48]Ho HN, Chao KH, et al. Peritoneal natural Killer cytotoxity and CD+3CD+25 lymphocyte subpopulation are decreased in women with stage Ⅲ～Ⅳ endometriosis. HumReprod,1995,10(10):2671
[1]Pizzo A, Salmeri FM, Ardita FV, et al. Behaviour of cytokine levels in serum and peritoneal fluid of women with endometriosis[J]. Gynecol Obstet Invest,2002, 54(2):82-87.
[2]KhamKN, MasazakiH, FujishitaA. Association of interleukin-6 and estradiol with hepatocye growth factor in peritoneal fluid of women with endometriosis. Acta Obstet Gynecol Scand,2002,81(8):764-771
[3]Iwabe T, Harada T, Sakamoto Y, et al. Gonadotropin-releasing hormone agonist treatment reduced serum interleukin-6 concentrations in patients'with ovarian endometrismas. Fertility and Sterility,2003,80(2):300-304
[4]Rapkin A, Morgan M, Bolpane C. Peritoneal fluid interleukin-6 in women with chronic pelvic pain Fertility and Sterility,2000.74(2):325-328
[5]Bedaiwy A, Falcone T. Sharma RK. Prediction of endometriosis with serum and peritoneal fluid markers:a prospective controlled trial. Hum Reprod,2002, 17(2):426-431
[6]Mulayim N, Savlu A, Guzeloglu K O, et al. Regulation of endometrial stromal cell matrix metalloproteinase activity and invasineness by interleukin-18[J]. Fertil Steril,2004,81(suppll):904-911
[7]Selam B, Kayisli U A, Garcia V J A, et.al. Regulation of fas ligand expression by IL-18 in human endometrium[J]. J Clin Endocrinol Metab,2002,87(8): 3921-3927
[8]Selam B, Kayisli UA, Garcia-Velasco JA, et al. Regulation of Fas ligand expression by IL-8 in human ndometrium [J]. J Clin Endocrinol Metab,2002, 87(8):3921-3927.
[9]Kitanwaki J, Oayashi H, Ohta M. Genetic contribution of the IL-10 promotor polymorphism in endometriosis suspetibility. Am J Reprod Immunol,2002, 47(1):12-18
[10]Yamanehi N, Hamda T, Tnaiugchi F, et la. Tumorv necrosis factor-alpha induced the release of interleukin-6 from endometriotic storma lcells by the nuclear factor-kappaB and mitogen-activated protein kinsae pathways. Fertil Steril, 2004,82[Supp]31:1023-102
[11]BraunDP, DingJ. GogaczM, etal. Regulation of endometrial cell apoptosis by TNFa is abnormal in women with endometriosis. Fertility and Strility,2002, 77, spl:sl
[12]Donald P, BraunD, JianchiD, etal. Peritoneal fluid mediated enhancement of eutopic and ectopic endometrial cell proliferation is dependent on tumor necrosis factor-alpha in women with endometriosis. Fertility and Sterility,2002,78(4):
727—732
[13]Na YJ, Yang SH, Baek DW, et al. Effects of peritoneal fluid from endometriosis patients on the release of vascular endothelial growth factor by neutrophils and monocytes [J]. HumReprod,2006,21(7):1846-1855.
[14]邱晓红,高秀艳,李荷莲.血管内皮生长因子在子宫内膜异位症组织中的表达,吉林大学学报(医学版),2002,28(2)：147-149
[15]曹树荣,罗仪,刘永珍.血管生长因子含量与子宫内膜异位症发病的关系.湖北民族学院学报,医学版,2002,19(2)：9-12
[16]Kim JG, Suh CS, Kim SH, et all. Insulin-like growth factors IGF-I binding proteins, and IGFBP-3 protease activity in the peritoneal fluid of patients with and endometriosis [J]. Fertil Steril,2000,73(5):996
[17]Antinolo G, Fernandez R M, Noval J A, et al. Analysis of the involvement of CCR5-Delta 32 and CCR2-V64I variants in the development of endometriosis[J]. Mol HumReprod,2004,10(3):155-157
[18]Akoum Al, Kong JH, Metz C, et al. Spontaneous and stimulated secretion of monocyte chemotatic protein-1 and mancrophase migration inhibitory factor by peritoneal macrophages in women with and without endometriosis. Fertility and Sterility,2002,77(5):989～994
[19]Kats R, Collette T, Metz CN, et al. Marked elevation of macrophage migration inhibitory factor in the peritoneal fluid of women with endometriosis. Fertil Steril,2002,78(1):69-76
[20]Morin M, Bellehumeur C, Therriault MJ, et al. Elevated levels of macrophage migration inhibitory factor in the peripheral blood of women with endometriosis. Fetril Steril,2005.83(4):865-872
[21]Arici A, Matalliotakis I, Goumenou A, et al. Increased levels of interleukin-15 in the peritoneal fluid of women with endometriosis:Inverse correlation with stage and depth of invasion.Hum Reprod 2003;18:429-432.
[22]Lebovic D I, Chao V A, Taylor R N. peritoneal macrophages induce RANTES(regulated on active, normal T cell expressed and secreted) chemokine gene transcription in endometrial stroma cells[J]. J Clin Endocrine Metab,2004, 89(3):1397-1401
[23]Bedaiwy MA, Falcone T, Sharma RK, et al. Prediction of endometriosis with serum and peritoneal fluid markers:A prospective controlled trial. Hum Reprod 2002; 17:426-431.
[24]Gineko P. The elevation of IL-12 levels in peritoneal fluid and serum of women with endometriosis. Hum Reprod,2001,72(5):408-417
[25]Koga K, Osuga Y, Yoshino O, et al. Elevated interleukin-16 levels in the peritoneal fluid of women with endometriosis may be a mechanism for inflammatory reactions associated with endometriosis[J]. Fertil Steril,2005, 83(4):878-882.
[26]Lochner M,Forster I.Anti-interleukin-18 therapyin murine models of inflammatory bowel disease [J]. Pathobiology,2002,70(3):164-169.
[27]Zhang XM, Lin J, Qian Y, et al. Decreased levels of interleukin-18 in peritoneal fluid but not in serum of patients with endometriosis. Fertility and Sterility,2004(5):1229-1234