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 (T(H)2)-type cytokines [i.e., interleukin (IL)-6, IL-10 , and IL-13] and transforming growth factor (TGF)-beta are expressed by tim e murine decidua and/or placenta and are likely to suppress inflammatory cy tokine [i.e., IL-2, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alp ha, IL-1 alpha and IL-1 beta] production at the maternal-fetal interface. I n addition, class I IFNs may protect the fetus from immunologic rejection a nd viral infections. This study examines the expression of inflammatory-imm unoregulatory cytokines and IL-IO production by first-trimester chorionic v illi. METHOD OF STUDY: Gestational tissues (n = 5) were obtained following electi ve terminations performed between 7 and 9 weeks of gestation. Chorionic vil lous 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 ge station) were maintained in organ culture, and human chorionic gonadotropin (hCG) and IL-10 levels were determined by immunoradiometric and enzyme-lin ked 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-alp ha 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. moder ate to high levels of IL-6 and IL-10 mRNA were detected in each chorionic v illous sample. In chorionic villous explants obtained at 6-11 weeks gestati on, 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: T(H)1-type cytokines (IL-2, IFN-gamma) are not expressed by fi rst-trimester chorionic villous tissues: This is possibly due to local prod uction of IL-IO. In contrast. macrophage-associated cytokines (IL-1 beta an d TNF-alpha) are expressed and their regulation may be critical for fetal s urvival. Finally, class I IFNs expressed by early chorionic tissues may pro tect the fetus from maternal rejection and viral transmission.