Theoretical basis for herbal medicines, Tokishakuyaku-san and Sairei-to, in the treatment of autoimmunity-related recurrent abortion by correcting T helper-1 T helper-2 balance

PROBLEM AND METHOD OF STUDY: To get insight into the basis for the empirical usage of herbal medicines in the treatment of recurrent abortion, we examined whether Tokishakuyaku-san (Toki) and Sairei-to (Sai) modulate T helper-1 (Th1) and T helper-2 (Th2) cytokine release from peripheral blood mononuclear cells (PBMCs). The effects of these medicines were investigated as related to human leukocyte antigen (KLA)-G, a non-classical HLA class I antigen expressed on trophoblasts and a putative crucial player involved in fetomaternal immune interplay. RESULTS: Toki and Sai increased the release of Th1 group cytokines, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma while preserving the inhibitory effect of HLA-G on the release of these cytokines. As for Th2 group cytokine release, Toki was without effect in modulating interleukin (IL)-4 release, regardless of the presence of HLA-G, whereas Sai nullified the effect of the presence of HLA-G to stimulate the release of IL-4 without affecting its release in the absence of HLA-G. CONCLUSION: Toki and Sai may have therapeutic potential, particularly in autoimmunity-related recurrent abortion where Th2 response is pathologically enhanced, but not in recurrent abortion involving alloimmune fetomaternal derangement, a condition of, rather, an enhanced Th1 response.