Immune alterations and endometriosis in rhesus monkeys following chronic dioxin exposure

We previously demonstrated that exposure to 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) is associated with a dose-dependent increase in the incidence and severity of endometriosis in the rhesus. Studies suggest that proinflammatory cytokines participate in dioxin toxicity and the pathogenesis of endometriosis. Hence, we characterized the phenotype, activational status and function of peripheral blood leukocytes (PBL) from TCDD-exposed (n=9) and unexposed rhesus monkeys (n=6). The profile of PBL was evaluated by flow cytometric analysis. Cytokine production by PBL and uterine endometrial cells was also determined. Absolute numbers of NK cells (CD16+/CD56+) were significantly increased in TCDD animals whilst PBL cytolytic activity was decreased relative to controls. A significant increase in activated CD3/CD25+ cells, and naive T cells (CD4+/CD45RA+), was also found in TCDD monkeys. PBL from TCDD animals Kad increased PHA-stimulated TNFa and IFN7 and spontaneous IL-6 production relative to controls. In contrast, PHA-stimulated IL-10 levels were lower following TCDD exposure. Uterine cells from a TCDD-exposed animal spontaneously secreted higher levels of TNFa and IL-6, coupled with decreased levels of IL-10, compared to control uterine cells. These studies suggest that TCDD exposure results in altered cytokine responses, both systemically and in the uterus, which may be related to the pathogenesis of endometriosis. This work was supported by the Endometriosis Association, Milwaukee WI, and NIH grants T32AI07363 and A134478.