Indoleamine 2,3-dioxygenase (IDO) activity in placental compartments of renal-transplanted pregnant women.

PROBLEM: Immunosuppressive drugs change gestational IDO activity at the maternal-fetal interface. METHOD OF STUDY: Analysis of placental IDO expression and activity, interferon gamma (IFN-γ), and IL-10 expression and NFkB activity in renal transplant recipient women under immunosuppressive treatment. RESULTS: We demonstrated a significant reduction in IDO activity (P = 0.0275) and expression (P = 0.026) and in NFkB activity (P = 0.0176) in the villous region of renal transplanted mother. These findings did not correlate with the higher serum levels of kynurenine (P = 0.002). In the decidual compartment, IDO was immunolocalized mainly on the extravillous cytotrophoblast but did not show significant differences among the experimental groups; kynurenine was significantly higher (P = 0.036) and was inversely proportional to the decidual IFN-γ profile (P = 0.0433). No change was seen in IL-10 levels. NFkB activity was significantly higher in decidual compartment correlating with the higher IDO activity and suggesting that in immunosuppressant pregnancy, IDO activity and expression remain regulated by NFkB. CONCLUSION: The increased IDO activity in decidua may indicate an attempt to offset the low expression. These findings call attention to the relevance of IDO activity at the maternal interface in pregnant transplant recipients, likely modulated by immunosuppressive agents and associated with a high risk of associated gestational disorders.

Compartmentalization of pro-inflammatory cytokine levels in renal-transplanted pregnant women.

OBJECTIVE: We evaluated whether chronic exposure to immunosuppression in transplant recipients modulate the placental inflammatory cytokine levels associated to gestational tolerance mechanisms. METHODS: Serum samples were collected from 12 renal transplanted pregnant under immunosuppressive regimen treatment and 10 healthy women in second/third trimester of gestation. Term placental tissues (decidua and chorionic villi) were also obtained after elective caesarean. Serum IL-1ß, IL-6, IL-8, IL-12p70 and TNF-α were measured, as also in placental homogenates, by Cytometric Bead Array (CBA) combined with flow cytometry and, TGF-ß and IL-18 were measured by ELISA. RESULTS: Serum levels of IL-6 (p = 0.0001) and TNF-α (0.0112) were higher in the 2nd and 3rd trimesters and in decidua the spectrum of increased pro inflammatory cytokines was wider: IL-1ß (p = 0.0001), IL-6 (p = 0.0001), IL-8 (p = 0.0001), IL-12p70 (p = 0.0001), TGF-ß (p = 0.0089) and TNF-α (p = 0.0002). TGF-ß1 was particularly increased in decidual compartment (p = 0.001). In the chorionic villous, pro inflammatory profile also were maintained. High IL-1ß (p = 0.0001), IL-6 (p = 0.0001), IL-8 (p = 0.0001) and TNF-α (p = 0.0001) levels establish a similar pattern to that seem in decidua. CONCLUSION: Immunosuppressors may impair the immune response, but when associated with pregnancy the cytokine levels seems to shift a proinflammatory profile in placental compartments, which might also impact on the gestational outcomes in transplanted mothers.