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 empirica l usage of herbal medicines in the treatment of recurrent abortion, we exam ined whether Tokishakuyaku-san (Toki) and Sairei-to (Sai) modulate T helper -1 (Th1) and T helper-2 (Th2) cytokine release from peripheral blood mononu clear cells (PBMCs). The effects of these medicines were investigated as re lated to human leukocyte antigen (KLA)-G, a non-classical HLA class I antig en expressed on trophoblasts and a putative crucial player involved in feto maternal immune interplay. RESULTS: Toki and Sai increased the release of Th1 group cytokines, tumor n ecrosis factor (TNF)-alpha and interferon (IFN)-gamma while preserving the inhibitory effect of HLA-G on the release of these cytokines. As for Th2 gr oup 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 a ffecting its release in the absence of HLA-G. CONCLUSION: Toki and Sai may have therapeutic potential, particularly in au toimmunity-related recurrent abortion where Th2 response is pathologically enhanced, but not in recurrent abortion involving alloimmune fetomaternal d erangement, a condition of, rather, an enhanced Th1 response.