Effects of Sairei-to and Tokishakuyaku-sa on cytokine release from peripheral blood mononuclear cells upon recognition of HLA-G protein in the treatment of recurrent abortion

Abstract

Human leukocyte antigen (HLA)-G has been shown to play a role in establishing pregnancy through the mechanism of modulating cytokine secretion from maternal lymphocytes. To elucidate the mechanisms of actions of the herbal medicines, Sairei-to and Tokishakuyaku-san, in the treatment of recurrent abortion, we investigated whether these medicines modulate cytokine secretion from peripheral blood mononuclear cells (PBMCs) upon recognition of HLA-G protein on trophoblasts. Sairei-to and Tokishakuyaku-san increased the interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha secretion and decreased the IL-3 secretion from PBMCs regardless of whether these cells recognized HLA-G protein or not. Accordingly, Sairei-to nullified the effects of HLA-G to reduce the secretion of IL-1 beta and TNF-alpha and to enhance the secretion of IL-3. Tokishakuyaku-san also abolished the effect of HLA-G to reduce IL-1 beta and TNF-alpha secretion but did not affect the increase in IL-3 secretion. Thus, it is conceivable that Sairei-to may normalize Th1/Th2 balance by enhancing Th1 polarization in autoimmunity-related recurrent abortion in which Th1/Th2 balance might be shifted towards Th2 polarization. However, the mechanisms of action of Tokishakuyaku-san when used in treating unexplained recurrent abortion, cannot be explained only by the Th1/Th2.