[O-311] PERIPHERAL AND LOCAL CYTOKINES INCLUDING IL-8, IL-9 AND IL-17 ARE ELEVATED IN ENDOMETRIOSIS: AN IN VIVO AND IN VITRO ANALYSIS BEFORE AND AFTER SURGERY SUGGESTS A MECHANISM FOR ENDOMETRIAL DYSFUNCTION.
B. A. Lessey, M. Nagarkatti, J. Zhou, S. L. Young, M. K. Adur, R. A. Nowak. Dept Obstet Gynecol Div REI, Univ South Carolina SOM Greenville, Greenville, SC; Dept Pathology, Microbiology and Immunology, Univ South Carolina School of Medicine Columbia, Columbia, SC; Dept Obstet Gynecology Div REI, University of North Carolina, Chapel Hill, NC; Animal Sciences, University of Illinois, Urbana, IL.
OBJECTIVE: We studied peripheral and local immune changes before and after excision of endometriosis compared to normal controls to better understand the association between endometriosis, inflammation and infertility.
DESIGN: Prospective analysis of blood, PF and endometrium before and after laparoscopy (L/S) and in vitro 3D co-culture of endometrial stromal cells (ESS) from normal and infertile women.
MATERIALS AND METHODS: We prospectively collected blood, uterine lavage, endometrium and peritoneal fluid before and after L/S performed for infertility and pain compared to fertile controls. Medium was collected and analyzed from Ishikawa cells co-cultured with ESS cells (plus E2 + MPA) in 3D culture. Bioplex 200 (Biorad, Inc) analysis of cytokines and FACS analysis was performed on peripheral blood, PF and endometrial leukocytes and culture medium. Immunohistochemistry (IHC) was performed on mid-secretory endometrium for Il-17 and FoxP3.
RESULTS: IL-1β, INF-γ, PDGF-bb, IL-8, IL-9, IL-17, G-CSF and FGF were all signficantly higher in plasma of endometriosis patients vs. controls with a significant drop in IL-9, INF-γ and IL-1β after L/S. INFγ and PDGF-bb changes were confined to blood, but IL-9 was elevated in PF, and IL-8 and MCP-1 increased in uterine lavage. ESS cells from endometriosis over-expressed IL-8 and IL-9 compared to controls (p < 0.01 and p < 0.05, respectively) in vitro. Corresponding changes in inflammatory leukocytes in blood and endometrium of cases vs. controls were noted by IHC and FACS analyses.
CONCLUSION: Specific, reversible differences in cytokines and leukocytes were noted in the peripheral blood, PF and endometrium in women with endometriosis. The novel finding of increased IL-9, a cytokine that promotes Th17 differentiation, may be central, along with IL-8, to infertility associated with endometriosis.
Supported by: This research was supported in part by NIH R01-068440 (SLY and BAL) and as well as grants to RN (U54 -HD40093) and MN (NIH R01 AT006888, R01 MH094755, R01 ES019313, P01, AT003961 and VA1 01BX001357).
Wednesday, October 24, 2012 4:45 PM
Oral Session: Endometriosis