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  • Title: Suppressive effect of a traditional Japanese medicine, Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan), on the hyperresponsiveness to IL-18 in autoimmune MRL/MPJ-lpr/lpr mice.
    Author: Furuya Y, Kawakita T, Nomoto K.
    Journal: Int Immunopharmacol; 2003 Mar; 3(3):365-73. PubMed ID: 12639814.
    Abstract:
    Oral administration of Hachimi-jio-gan (HMG, Ba-Wei-Di-Huang-Wan), a traditional Japanese herbal medicine, for several weeks, ameliorates some autoimmune symptoms of MRL/lpr mice. In the short time treatment for 9 days, hyperresponsiveness of mesenteric lymph node (MLN) cells to interleukin (IL)-18 manifested by the proliferation or the production of interferon (IFN)-gamma was significantly suppressed. Additionally, the treatment with HMG suppressed the expressions of IL-18Ralpha and IL-18Rbeta mRNA in CD45R(-) T cells, and also the expression of IL-18Ralpha mRNA in unpurified whole cells. Although the short treatment with HMG had no effect on the mRNA expressions of IL-10, IL-12 and IL-18, or the phosphorelated signal transducer and activator transcription (STAT)4 protein level in CD45R(-) MLN cells, the IL-4 mRNA expression or the phosphorelated STAT6 protein level were up-regulated by HMG, and the IL-4 mRNA up-regulation was clearer in whole cells than CD45R(-) cells. Furthermore, the treatment with HMG promoted the mRNA expression of invariant Valpha14 TCR that is uniquely expressed on NKT cells. Valpha14 NKT cells can produce large amount of IL-4 and play a crucial role in controlling the development of MRL/lpr mouse autoimmune disease. Therefore, these results suggested that HMG reduced the hyperresponsiveness of MRL/lpr mouse MLN cells to IL-18 through the reduction of IL-18Rs caused by Valpha14 NKT cell-produced IL-4, and consequently HMG suppressed the development of MRL/lpr autoimmune diseases.
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