Thymus-dependent effects of a traditional chinese medicine, ren-shen-yang-rong-tang (Japanese name; Ninjin-Youei-To), in autoimmune MRL/MP- Ipr/Ipr mice

Abstract

Autoimmune MRL /lpr mice were i.p. treated with 200 mg/kg Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NYT), a traditional Chinese herbal medicine (Japanese name: Kampo), from 8 weeks of age every 3 days before the onset of autoimmune disease. Compared to age-matched control MRL /lpr mice, the serum IL-6 concentration in NYT-treated mice was decreased, their serum IFN-γ concentration was increased, and the proliferative responses of whole and enriched CD4 + cells in their spleen and lymph nodes stimulated with ConA in vitro were restored. FACS analysis revealed that the rate of decreased CD4 +CD8 + T-cell population in the thymus was decreased in MRL /lpr mice but recovered by NYT treatment. Further, adult thymectomized (ATX) MRL /lpr mice were treated with 200 mg/kg NYT similarly. NYT treatment prolonged the survival of sham-operated MRL /lpr mice and ameliorated their proteinuria but did not improve such autoimmune manifestations in ATX-MRL /Ipr mice. These findings suggest that NYT plays an important role in the abrogation of autoimmune-prone T cell differentiation and that the therapeutic effect of NYT is dependent on the thymus in MRL /Ipr mice.