Interleukin-1 receptor antagonist-based immunotherapy on autoimmune diabetes

• Main Author: 廖健翔
• Other Authors: Huey-Kang Sytwu
• Format: Others
• Language: zh-TW
• Published: 2000
• Online Access: http://ndltd.ncl.edu.tw/handle/03410938336018266922

碩士 === 國防醫學院 === 微生物及免疫學研究所 === 88 === Insulin-dependent diabetes mellitus (IDDM) is caused by a progressive autoimmune destruction of the insulin-producing b cells in the pancreatic islets of Langerhans. Both genetic predisposition and environmental factors contribute to its pathogenesis. A widely used animal model for dissecting immunopathological mechanisms in IDDM and for developing preventive and/or therapeutic strategies is the non-obese diabetic (NOD) mouse, an inbred strain that spontaneously develops an autoimmune diabetes resembling human IDDM. Interleukin-1b (IL-1b), a potent pro-inflammatory cytokine, has been shown to mediate the autoimmune diabetic process and to trigger the destruction of b cells in several animal models. Blocking the IL-1b bioactivity by IL-1 receptor antagonist (IL-1ra) or monoclonal anti-IL-1b has been reported by our laboratory to inhibit the disease process on the delay onset of diabetes or the decrease of disease frequency. Since naked nucleic acid vectors carrying cytokine genes are potentially useful candidates for the prevention/treatment of autoimmune diseases, we seek to treat/prevent autoimmune diabetes by injecting IL-1ra-expressing vectors. Our results show a significant protection from cyclophosphamide-induced diabetes in NOD mice intramuscularly or intravenously injected with pcDNA-IL-1ra vector. We also observed a slight decrease of delayed-type hypersensitivity reaction and a moderate inhibition of host defense against bacterial infection in those IL-1ra-treated mice. Despite these potential side-effects, IL-1ra DNA therapy could be very useful for autoimmune diabetes.