Murine abortion is associated with enhanced interleukin-6 levels at the feto-maternal interface

Abstract

CBA/JXDBA/2J murine abortion is known to be associated with increased local and peripheral Th1-cytokines levels. The role of the pro-inflammatory interleukin-6 (IL-6) in murine abortion remains unclear. In humans, IL-6 was reported to be elevated at the onset of spontaneous abortion. The aim of our study was to evaluate the levels of IL-6 during murine pregnancy in (1) the normal murine pregnancy combination CBA/JXBALB/c and in (2) the CBA/JXDBA/2J abortion prone mating combination. We measured IL-6 serum levels by ELISA and local (placental and decidual) IL-6 levels by flow cytometry and immunohistochemistry. The expression of the IL-6 receptor gp80 was further analyzed. We additionally evaluated the number of mast cells and macrophages at the feto-maternal interface as a putative IL-6 source in reproductive tissues. IL-6 and gp80 were expressed in decidual cells as well as in different trophoblast types. Flow cytometry analysis showed increased numbers of IL-6+ cells in abortion placentas and deciduas compared to control pregnant mice. We observed an elevated number of mast cells and macrophages at the feto-maternal interface from abortion mice in comparison to control mice. Interestingly, we found very high numbers of mast cells, macrophages and IL-6+ cells in resorption tissue compared to control tissues. Flow cytometry studies confirmed that macrophages are being an important source of IL-6 at the feto-maternal interface. The mRNA IL-6 levels were also enhanced in placenta and decidua from mice with high abortion rate compared to normal pregnant mice, as analyzed by RT-PCR. Our results suggest that IL-6 produced not only by immunocompetent cells such as macrophages and mast cells, but also by trophoblasts and decidua cells, is directly involved in the pathology of abortion.