First-Trimester Human Chorionic Villi Express Both Immunoregulatory and Inflammatory Cytokines: A Role for Interleukin-10 in Regulating the Cytokine Network of Pregnancy

Authors


Division of Research, Department of Obstetrics and Gynecology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505.

Abstract

PROBLEM: T-helper 2 (TH2)-type cytokines [i.e., interleukin (IL)-6. IL-10, and IL-13] and transforming growth factor (TGF)-β are expressed by the murine decidua and/or placenta and are likely to suppress inflammatory cytokine [i.e., IL-2, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-1α, and IL-1β] 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-γ and IL-2 were generally not expressed by first-trimester chorionic villi. Low to moderate levels of expression were noted for IL-1α, IL-1β, and TNF-α. High levels of mRNA were noted for IFN-α and IFN-β, but IFN-τ was not expressed. In all tissues. TGF-β1 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-γ) 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-1β and TNF-α) are expressed and their regulation may be critical for fetal survival. Finally, class I IFNs expressed by early chorionic tissues may protect the fetus from maternal rejection and viral transmission.

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