Abstract
Human chorionic gonadotrophin (hCG) is a hormone produced during pregnancy and present at the implantation site and in the maternal blood. Pregnancy has been proposed to represent a controlled state of inflammation at an early stage at the implantation site and later, systemically extended to the maternal circulation. Earlier, we reported that hCG can inhibit the development of diabetes in NOD mice and LPS-induced septic shock in a murine model. We hypothesize that hCG can contribute to the reduction of inflammation by modifying Mphi function. Here, the TG-induced peritonitis model for inflammation was used to investigate the effect of hCG on cytokine production and cell recruitment in vivo. hCG pretreatment in TG-induced peritonitis increased the number of peritoneal cells, especially PMN and monocytes, compared with mice injected with TG only. This increased cell number was partially explained by increased cell survival induced by hCG. Despite the cellular infiltrate, hCG pretreatment decreased i.p. TNF-alpha, IL-6, PTX3, CCL3, and CCL5 levels. By depleting peritoneal resident Mphi using clodronate liposomes prior to the application of hCG and the TG trigger, we established that Mphi are the main responsive cells to hCG, as the suppressed TNF-alpha and IL-6 production and increased PMN influx are abolished in their absence. Together, these data suggest that hCG contributes to the controlled inflammatory state of pregnancy by regulating Mphi proinflammatory function.