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

• Published in: American journal of reproductive immunology (1989) 1999-01, Vol.41 (1), p.70-78
• Main Authors: Bennett, William A., LagooDeenadayalan, S., Whitworth, N.S., Stopple, J.A., Barber, W.H., Hale, E., Brackin, M.N., Cowan, B.D.
• Format: Article
• Language: English
• Subjects: Abortion, Induced; Biological and medical sciences; Cell physiology; Chorionic Gonadotropin - biosynthesis; chorionic villi; Chorionic Villi - immunology; Chorionic Villi - metabolism; Cytokines; Cytokines - metabolism; Enzyme-Linked Immunosorbent Assay; expression; Female; Fundamental and applied biological sciences. Psychology; Humans; Immune Tolerance; immunotolerance; Interleukin-10 - biosynthesis; Interleukin-10 - physiology; Molecular and cellular biology; Organ Culture Techniques; pregnancy; Pregnancy - immunology; Pregnancy Trimester, First; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Messenger - metabolism; Secretion. Exocytosis
• ISSN: 1046-7408; 8755-8920; 1600-0897
• DOI: 10.1111/j.1600-0897.1999.tb00077.x

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.