Blood soluble interleukin 1 receptor accessory protein levels are consistently low throughout the menstrual cycle of women with endometriosis

BACKGROUND: A deficiency in the counter-regulatory mechanisms of interleukin 1 (IL1) may play a significant role in endometriosis pathogenesis and associated chronic inflammation. The aim of this study was to investigate peripheral blood levels of soluble IL1 receptor accessory protein (sIL1RAP), a potent natural inhibitor of IL1, in women with and without endometriosis. METHODS: Peripheral blood samples were collected from women with endometriosis (n = 47) consulting for infertility, pelvic pain or tubal ligation, in whom the disease was diagnosed at laparoscopy. Control healthy women (n = 27) were requesting tubal ligation or reanastomosis and had no visible evidence of endometriosis at laparoscopy. sIL1RAP levels were determined by ELISA, whereas estradiol (E2) and progesterone (P4) levels were determined by competitive immunoassays. RESULTS: sIL1RAP levels were significantly decreased in women with early endometriosis stages compared to controls (p < 0.05) and markedly during the proliferative phase of the menstrual cycle (p < 0.001). Actually, while sIL1RAP were significantly increased in the proliferative compared to the secretory phase in normal women (p < 0.0001) and peaked at the end of this phase, sIL1RAP remained consistently low and showed non-significant variations throughout the menstrual cycle in women with endometriosis. CONCLUSIONS: Lower circulating levels of sIL1RAP points to a significant impairment in the counter-regulatory mechanisms of IL1, which in view of the cytokine’s potent inflammatory and growth-promoting properties may play a significant role in the pathophysiology of endometriosis

Macrophage Migration Inhibitory Factor Antagonist Blocks the Development of Endometriosis In Vivo

Endometriosis, a disease of reproductive age women, is a major cause of infertility, menstrual disorders and pelvic pain. Little is known about its etiopathology, but chronic pelvic inflammation is a common feature in affected women. Beside symptomatic treatment of endometriosis-associated pain, only two main suboptimal therapeutic approaches (hormonal and invasive surgery) are generally recommended to patients and no specific targeted treatment is available. Our studies led to the detection of a marked increase in the expression of macrophage migration inhibitory factor (MIF) in the eutopic endometrium, the peripheral blood and the peritoneal fluid of women with endometriosis, and in early, vascularized and active endometriotic lesions. Herein, we developed a treatment model of endometriosis, where human endometrial tissue was first allowed to implant into the peritoneal cavity of nude mice, to assess in vivo the effect of a specific antagonist of MIF (ISO-1) on the progression of endometriosis and evaluate its efficacy as a potential therapeutic tool. Administration of ISO-1 led to a significant decline of the number, size and in situ dissemination of endometriotic lesions. We further showed that ISO-1 may act by significantly inhibiting cell adhesion, tissue remodeling, angiogenesis and inflammation as well as by altering the balance of pro- and anti-apoptotic factors. Actually, mice treatment with ISO-1 significantly reduced the expression of cell adhesion receptors αv and ß3 integrins (P<0.05), matrix metalloproteinases (MMP) 2 and 9 (P<0.05), vascular endothelial cell growth factor (VEGF) (P<0.01), interleukin 8 (IL8) (P<0.05), cyclooxygenease (COX)2 (P<0.001) and the anti-apoptotic protein Bcl2 (P<0.01), but significantly induced the expression of Bax (P<0.05), a potent pro-apoptotic protein. These data provide evidence that specific inhibition of MIF alters endometriotic tissue growth and progression in vivo and may represent a promising potential therapeutic avenue

Mise en evidence d'un nouvel anticoagulant, secrete par Myxococcus xanthus, la myxaline : caracterisation et etudes in vitro de ses proprietes biologiques

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

L’implantation embryonnaire

La réceptivité de l’endomètre à l’embryon représente un élément essentiel de l’implantation embryonnaire, que la fécondation ait été naturelle ou via une procédure médicalement assistée. Ainsi, le taux moyen d’implantation des embryons conçus par fécondation in vitro reste faible (20-25 %). Même si de nombreux progrès ont été accomplis en procréation médicalement assistée, l’implantation, qui implique des régulations croisées de type endocrinien et immunitaire, requiert une coordination étroite entre tissus maternels et embryonnaires, qui reste encore très mystérieuse. Un dialogue précoce entre la mère et l’embryon est donc essentiel pour synchroniser ces régulations et assurer l’implantation du blastocyste au sein de l’endomètre. Les facteurs maternels, tels que les hormones stéroïdiennes, les enzymes dégradant la matrice tissulaire, les intégrines, les cytokines, les chimiokines et de nombreux facteurs de croissance embryonnaires, pourraient être impliqués dans ce dialogue fœto-maternel. Parmi les cytokines, certains membres de la famille de l’interleukine 1 participent à la mise en place, au sein de l’endomètre, d’un environnement propice à l’implantation embryonnaire et au développement de l’embryon. Ces données récentes pourraient permettre l’identification de marqueurs fiables de la réceptivité endométriale maternelle