Human Anti-Human IL1R2 monoclonal Antibody, clone SFB855 [Biotin]

Objective: To evaluate the levels of interleukin-1 beta (IL1 beta) and its inhibitory soluble interleukin-1 receptor type II (IL1R2) in the peritoneal fluid (PF) of normal women and patients with endometriosis suffering from pelvic pain and infertility. Design: Retrospective study using ELISA to measure peritoneal fluid IL1 beta and soluble IL1R2. Setting: Gynecology clinic and human reproduction research laboratory. Patient(s): Sixty-eight normal women and 154 women with endometriosis. Intervention(s): Peritoneal fluid samples were obtained at laparoscopy. Main Outcome Measure(s): IL1 beta and soluble IL1R2 concentrations in the PF samples. Result(S): This study showed a marked decrease in peritoneal soluble IL1R2 levels in women with endometriosis compared to normal women and a concomitant increase in the levels of IL1 beta. Both fertile and infertile women with endometriosis had lower soluble IL1R2 and higher IL1 beta concentrations than fertile women having a normal gynecological status, but the difference was more significant in infertile endometriosis patients. Compared with normal controls, the decrease in soluble IL1R2 levels was less significant in women with endometriosis than without pelvic pain, whereas the increase in IL1 beta concentrations was statistically significant only in women with endometriosis reporting pelvic pain. Conclusion(S): This study revealed an imbalance between IL1 beta and its decoy inhibitory receptor type 2 in women with endometriosis, which was particularly obvious in those who were infertile, and suggests that a defect in the local control of IL1 may be involved in the pathophysiology of endometriosis and related infertility. (Fertil Sterile 2008;89:1618-24. (c) 2008 by American Society for Reproductive Medicine.).

Secretion of embryonic IL-1 beta seems to be the first response of the blastocyst to receptive endometrium, inducing molecular changes that are essential for attachment of the blastocyst. Here, we report that human chorionic gonadotropin (hCG), a glycoprotein hormone that plays a critical role in the initiation and maintenance of pregnancy, markedly down-regulates the expression of the decoy inhibitory IL-1 receptor type II (IL-1R2) in human endometrial epithelial cells. Treatment with hCG resulted in a dose-dependent decrease in IL-1R2 soluble and membrane bound protein forms and mRNA steady-state levels, whereas no significant effect on the expression of the activating IL-1 receptor type I (IL-1R1) was seen. Cell infection with the wild-type human LH/chorionic gonadotropin receptor corroborated the aforementioned data, whereas cell infection with the constitutively activated LH chorionic gonadotropin receptor led to similar effects on IL-1R2 and IL-1R1 expression without hCG treatment. Cloning of human IL-1R2 gene promoter in the pGL3 luciferase reporter vector and transient transfection experiments further showed a significant dose-dependent diminution of IL1R2 promoter activity in response to hCG. These data suggest that hCG, by down-regulating the expression of IL-1R2, a potent and specific inhibitor of IL-1, without affecting the expression of the functional activating IL-1R1, diminishes the ability of endometrial epithelial cells to counterbalance the local effects of IL-1, making these cells probably more responsive to the cytokine. In view of IL-1's role as an embryonic signal, these data reveal a new mechanism by which hCG sustains human pregnancy and promotes embryonic growth.