In-Vivo Immune Modulating Effects of the Human Chorionic Gonadotropine Hormone.

Human chorionic gonadotropine (hCG) is a naturally occurring immune modulating agent, which is highly expressed during pregnancy. It is often observed that during pregnancy some autoimmune diseases such as multiple sclerosis and Crohn’s disease improves in women. Here we hypothesized that the improvement might be associated with HCG expression during pregnancy and evaluated its possible immunemodulating effects. Blood samples obtained from 34 women (median age 37, range 18–47) who underwent in-vitro fertilization (IVF) and received therefore HCG subcutaneously at three different time points (10.000 IE first, after 24 hours 5000IE, after 48 hours 5000IE) were examined prior and after HCG application. Thereafter skin transplantation was performed with HCG and without in mice. We noticed a significant increase of the number of Tr cells (CD4+CD25+) to up to 40% (p<0.04) after the first and second hCG application in the blood samples of women. A twofold increased of CTLA-4 expression after the first hCG application (p<0.049) was observed, whereas at the same time FoxP3 expression fell rapidly (p<0.006). Our analysis of Th1 (CD3+CD4+IFNγ) and Th2 (CD3+CD4+IL4+) type T cells revealed a slight shift after hCG application: the number of Th1 cells did not alter significantly, whereas the number of Th2 cells increased significantly (p<0.048). Further analyses showed that other subpopulations including B cells (CD19+), NK cells (CD16+CD56+), T helper cells (CD3+CD4+; CD3+CD4+CD45RA; CD3+CD4+CD45RO+), cytotoxic T cells (CD3+CD4+CD8+), TCRab and TCRgd positive T cells were not influenced by hCG. Also, we analyzed cytokine serum levels in women before and after each hCG application by ELISA. Hereby we found that two applications of hCG increased serum levels of both IL-8 and IL-10 significantly (p<0.013 and p<0.03, respectively) measured by ELISA assays (p<0.013), whereas the serum levels for IL-2, IL-4, TNF-α, IFN-γ, TGF- β and IL-1β (data not shown) were not significantly altered by hCG. HCG application increased the expression of anti-inflammatory interleukin-27 (IL-27) and reduced that of the inflammatory IL-17. In addition, we found increased IL-10 serum levels and increased numbers of regulatory T cells CD4+CD in peripheral blood of women after hCG application. Rejection of BALB/c skin grafts transplanted in B6 mice was significantly delayed when mice received hCG after transplantion. We conclude that hCG may be useful for the induction of immune tolerance in allogeneic transplantation.