Herbal medicines, Sairei-to and Tokishakuyaku-san, differently modulate the release of cytokines from decidual versus peripheral blood mononuclear cells

PROBLEM AND METHOD OF STUDY: We have shown that Tokishakuyaku-san (Toki) and Sairei-to (Sai) enhance T helper-1 (Th1) cytokine release from peripheral blood mononuclear cells (PBMCs); thereby, they could be a therapeutic means in the treatment of autoimmunity related recurrent abortion in which T helper-2 (Th2) polarization is exaggerated, the condition purported to benefit from these herbal medicines. However, an open question is whether these medicines might enhance Th1 cytokine release in decidual tissues and thereby stimulate the killer activity, thus, working counterproductively by accelerating maternal alloimmune reactions toward fetal tissues. To address this, we examined the effects of these medicines on the release of cytokines from decidual mononuclear cells (DMCs) in comparison with PBMCs on the assumption that they might act differently on these cell types. The effects of these medicines were investigated as related to human leukocyte antigen (HLA)-G, a nonclassical HLA class I antigen expressed on trophoblasts and a putative crucial player involved in fetomaternal immune interplay. RESULTS: Regarding Th1 cytokines, Toki marginally increased the release of tumor necrosis factor (TNF)-alpha, but not interferon (IFN)-gamma from DMCs while Sai did not affect the release of both. Both Toki and Sai were without effect in modulating the release of interleukin (IL)-4, a member of Th2 cytokines. Interestingly, the presence of HLA-G reduced the release of Th1 cytokines from DMCs regardless of the addition of Toki, Sai or none. These findings are in sharp contrast with PBMCs on which these medicines seem to act so as to enhance Th1 polarization and attenuate Th2 polarization. CONCLUSION: Differential effects of Toki and Sai on the release of Th1/Th2 cytokines between DMCs and PBMCs may afford the rationale of these medicines in the treatment of autoimmunity-related recurrent abortion.