The role of sex hormone regulation in Concanavalin A-induced hepatitis in mice.

• Main Authors: Li-Heng Kuo, 郭俐亨
• Other Authors: Huan-Yao Lei
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/46677621822670132065

碩士 === 國立成功大學 === 微生物及免疫學研究所 === 91 === An inflammation-mediated liver disease, both acute and chronic hepatitis, represents a worldwide health problem in human beings, and chronic hepatitis is associated strongly with the development of hepatocellular carcinoma. Experimental animal models have been used for a long time to study liver-specific immune regulation. Concanavalin A ( Con A ) — induced hepatitis in mice is thought to mimic the autoimmune hepatitis in human. The degree of autoimmune hepatitis is known to be different between genders — female is severe than male. In this study, we used the Con A-induced hepatitis model to investigate the role of sex hormones in autoimmune hepatitis. Con A is a lectin from plant, it binds specifically to certain sugar residues on T cell surface glycoproteins such as TCR or CD3 molecules and then stimulates the T cells to proliferate. It is known as a mitogen for T lymphocytes. When different strains of mice were given a single intravenous injection of Con A (10 mg/kg ). The acute hepatic injury assessed by increased plasma transaminase levels developed within 24 hours and lasted until 36 or 48 hours. The severities of liver injury were different among different strains and gender. C57BL/6 and BALB/c mice were more sensitive to Con A-induced hepatitis than A/J mice. The Con A-induced hepatitis is more severe in female mice than in male mice. The number of T lymphocytes in the liver was increased after Con A injection, especially the CD4+ T cells. There were more infiltrated CD4+ and CD8+ T cells in female than in male mice. We are interested in the hormonal regulation of this hepatitis model. Female mice were ovariectomized for two weeks, then challenged with Con A. The plasma transaminase levels of these levels of these ovariectomized mice were reduced to those of male mice. However after the estrogen supplement in these ovariectomied mice, the severity of Con A-induced hepatitis could be restored to the level of female mice. The CD4+ and CD8+ infiltrating T cells were increased significantly in estradiol supplemented ovariectomied mice compared to ovariectomied non-supplemented mice. The cytokines of IL-4, IL-6, IL-10, IL-12, TNF-α and IFN-γ in liver after Con A stimulation were found higher in female or estradiol supplemented ovariectomized mice than male or ovariectomized mice. Furthermore, the natural killer T (NKT) cells in liver were different in different genders of mice. After Con A stimulation, the number of these NKT cells changed as well. This suggests that NKT may also be affected by estradiol in this Con A-induced hepatitis.