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Keywords:

  • Decidua;
  • IL-16;
  • IL-17;
  • IL-18;
  • placenta;
  • Th1/Th2 paradigm

PROBLEM:  To determine if interleukin-16 (IL-16), IL-17, and IL-18 are present at the murine fetomaternal interface during pregnancy as a first step towards investigating their roles in fetomaternal relationship.

METHODS:  Expression of IL-16, IL-17, and IL-18, was assessed by immunohistochemistry (IHC) in the BALB/c × BALB/k (H2d × H2k), and the CBA/J × BALB/c non-abortion prone, and CBA/J × DBA/2 abortion prone matings. Enzyme-linked immunosorbent assay (ELISA) were performed for the two latter cytokines to compare local production in the abortion prone CBA/J × DBA/2 versus the non-abortion prone CBA/J × BALB/c matings.

RESULTS:  Expression of IL-17 was borderline. The anti-IL-16 staining specifically localized in the uterine stroma and glandular epithelium and was rather low in the placenta. IL-18 staining started in the peri-implantation uterus in the basal proliferative stroma, and was also traced, although weaker, in the glandular epithelium. In the immediate post-implantation period, a weak stromal staining persisted but there was a strong labeling of the ectoplacental cone. Interestingly, when the ectoplacental cone differentiates into placenta having a major histocompatibility complex (MHC) class I+ spongiotrophoblast and a (MHC class I–) labyrinth, a very strong transient labeling of uterine natural killer (u-NK) cells was found. Later in gestation, IL-18 was also produced by giant cell and spongiotrophoblast. Finally, we compared by ELISA the production of IL-17/-18 in CBA/J × DBA/2 and CBA/J × BALB/c matings. We detected significantly more IL-18 in the non-abortion prone combination decidua or placenta.

CONCLUSION:  The three cytokines IL-16, IL-17, and IL-18 were detected at the fetomaternal interface with a tissue specific, stage-dependent distribution. The predominance of IL-18 secretion in the non-resorption prone matings lead us to question the general validity of the classical T-helper (Th)1/2 paradigm.