Effects of sairei-to and tokishakuyaku-san on cytokine release from peripheral blood mononuclear cells upon recognition of HLA-G protein in the treatment of recurrent abortion.
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.
Fujii
T
T
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Tokyo, Japan. fujiit-tky@umin.ac.jp
Hamai
Y
Y
Kozuma
S
S
Miki
A
A
Yamashita
T
T
Hyodo
H
H
Unno
N
N
Taketani
Y
Y
D000026:Abortion, Habitual / Q000517:prevention & control*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000032:analysis; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D008517:Phytotherapy; D010946:Plants, Medicinal / Q000627:therapeutic use*; D011247:Pregnancy; D014327:Trophoblasts / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha