Unique therapeutic effects of the Japanese-Chinese herbal medicine, Sairei-to, on Th1/Th2 cytokines balance of the autoimmunity of MRL/lpr mice.
Sairei-to, one of the Japanese-Chinese herbal medicines has been used for the treatment of various diseases, especially collagen disease and edema in nephrotic syndrome. However, the mechanism of the therapeutic effects remains uncertain. Therefore, we investigated the immunological changes of skin, kidney, spleen cells and serum in autoimmune-prone MRL/lpr, MRL/n and C57BL/6J mice treated with Sairei-to. In MRL/lpr mice treated with Sairei-to, the improvement of proteinuria, reduction in the number of hematoxylin bodies in kidney, and reduced serum levels of blood urea nitrogen were observed. These results indicate that Sairei-to can improve or inhibit the progression of lupus nephritis. The proportion of CD19 and the serum levels of IgG1, which is one of the pathogenesis of lupus dermatoses and lupus nephritis, were significantly reduced in Sairei-to-treated MRL/lpr mice. Therefore, it is suspected that the B cell function was suppressed by Sairei-to. In addition, CD4/8 ratio in spleen cells and the degree of lymphoproliferation in MRL/lpr mice also decreased. Interestingly, IL-4 producing spleen cells were increased significantly by ELISPOT assay, and IFN-gamma mRNA expressions were reduced in Sairei-to-treated MRL/lpr mice. Regarding the Th balance, an imbalance towards Th1 predominance may play a significant role in MRL/lpr mice, and the Th1 axis was suppressed and the Th2 axis became predominant in Sairei-to-treated MRL/lpr mice. On the other hand, Th2 cell type immunoglobulins (IgG1) were suppressed. These results suggested that Sairei-to is potential for impairing shifted Th1/Th2 balance and hypergammaglobulinemia resulting in therapeutic effects.
Ito
Taisuke
T
Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. itoutai@hama-med.ac.jp
Seo
Naohiro
N
Yagi
Hiroaki
H
Ohtani
Toshio
T
Tokura
Yoshiki
Y
Takigawa
Masahiro
M
Furukawa
Fukumi
F
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects* / Q000502:physiology*; D001806:Blood Urea Nitrogen; D016516:CD4-CD8 Ratio; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007136:Immunoglobulins / Q000097:blood; D007150:Immunohistochemistry; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D009929:Organ Size / Q000187:drug effects; D010641:Phenotype; D011507:Proteinuria / Q000652:urine; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D016207:Cytokines; D004365:Drugs, Chinese Herbal; D007136:Immunoglobulins; D012333:RNA, Messenger; C080903:sairei-to