First-trimester human chorionic villi express both immunoregulatory and inflammatory cytokines: a role for interleukin-10 in regulating the cytokine network of pregnancy.
PROBLEM: T-helper 2 (TH2)-type cytokines [i.e., interleukin (IL)-6, IL-10, and IL-13] and transforming growth factor (TGF)-beta are expressed by the murine decidua and/or placenta and are likely to suppress inflammatory cytokine [i.e., IL-2, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, IL-1 alpha, and IL-1 beta] production at the maternal-fetal interface. In addition, class I IFNs may protect the fetus from immunologic rejection and viral infections. This study examines the expression of inflammatory/immunoregulatory cytokines and IL-10 production by first-trimester chorionic villi. METHOD OF STUDY: Gestational tissues (n = 5) were obtained following elective terminations performed between 7 and 9 weeks of gestation. Chorionic villous tissues were separated from fetal membranes and decidua, and total RNA was extracted. Cytokine expression was assessed by a reverse transcriptase-polymerase chain reaction technique. Chorionic villi (n = 9; 6-12 weeks gestation) were maintained in organ culture, and human chorionic gonadotropin (hCG) and IL-10 levels were determined by immunoradiometric and enzyme-linked immunosorbent assays, respectively. RESULTS: IFN-gamma and IL-2 were generally not expressed by first-trimester chorionic villi. Low to moderate levels of expression were noted for IL-1 alpha, IL-1 beta, and TNF-alpha. High levels of mRNA were noted for IFN-alpha and IFN-beta, but IFN-tau was not expressed. In all tissues, TGF-beta 1 and IL-13 were either weakly expressed or not expressed. In contrast, moderate to high levels of IL-6 and IL-10 mRNA were detected in each chorionic villous sample. In chorionic villous explants obtained at 6-11 weeks gestation production of hCG and IL-10 was greatest during the first 24 hr ([hCG] = 6961 +/- 815 mIU/mL, [IL-10] = 92 +/- 11 pg/mL) and then declined through 72 hr. CONCLUSIONS: TH1-type cytokines (IL-2, IFN-gamma) are not expressed by first-trimester chorionic villous tissues: This is possibly due to local production of IL-10. In contrast, macrophage-associated cytokines (IL-1 beta and TNF-alpha) are expressed and their regulation may be critical for fetal survival. Finally, class 1 IFNs expressed by early chorionic tissues may protect the fetus from maternal rejection and viral transmission.
Bennett, WA; Lagoo-Deenadayalan, S; Whitworth, NS; Stopple, JA; Barber, WH; Hale, E; Brackin, MN; Cowan, BD
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