|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1993 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1992 : ¥1,500,000 (Direct Cost : ¥1,500,000)
I summarized the results of these investigations. First, we examined the efficacy of biochemical and histology after more than 4 yrs of ursodeoxycholic acid(UDCA)treatment in primary biliary chirrhosis(PBC). Three cases show that liver histology was found to be improved, as were blood chemistry and pruritus, during short-term UDCA treatment, but histology results were slightly worse after long-term treatment despite the sustained improvement in biochemistry and pruritus. Moreover, consistent changes of MHC class I and II antigens by UDCA were not obtained. It is supposed that UDCA is not fundamental treatment, but delay the progression of the clinical stage of PBC.Second, we studied wherther the amount of soluble MHC class I antigen shows the relation between the mortality of GVHR.Our results indicates that measurement of soluble MHC calss I antigen is uesful for deciding the severity of GVHR.Third, we examined the effect of interleukin-6(IL-6) on the development of autoimmune diseases employing murine GVHR model with MHC class II disparity. Autoimmune like lesions in transgenic recipients became weakened as compared with those in non-transgenic recipients. In contrast, anti-PDH antibody in transgenic recipients were significantly higher than that of non-transgenic recipients. These results indicate that IL-6 excessively produced in vivo might regulate the progression of autoimmune diseases. In the last study, in order to elucidate the UDCA effect mechanisms, we studied the cellular immunological changes after UDCA and TUDCA treatment in MHC class II mutant mice. We could not recognize that the degree of GVHR, the expression of MHC class II, CD4/CD8 ratio and ICAM-1 between treatment group and non-treament group. In the PBC model, it is supposed that UDCA may not regulate the cellular immunity. Further studies regarding the soluble MHC calss I level and IL-6 in PBC patients, are needed.