THERAPEUTIC STUDIES IN MURINE LUPUS

小鼠狼疮的治疗研究

• 批准号: 3819291
• 负责人: A D STEINBERG
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3819291
• 关键词: autoimmune disorder; connective tissue disorder chemotherapy; corticosteroids; cyclophosphamide; genetic strain; immunogenetics; immunopathology chemotherapy; laboratory mouse; leukocyte activation /transformation; systemic lupus erythematosus; tumor necrosis factor alpha

Cyclophosphamide is effective therapy for murine lupus. MRL-lpr/lpr mice treated with corticosteroids from 3 months of age did not achieve significantly prolonged survival. Others have reported that tumor necrosis factor alpha (TNF) deficiency is a fundamental defect in murine lupus and that replacement therapy is very effective in preventing disease. We have treated BXSB males, MRL-lpr/lpr mice of both sexes and (NZB x NZW)Fl mice with TNF after the onset of disease manifestations. Such therapy was of modest benefit. Lymphadenopathy was reduced in MRL-lpr/lpr mice but survival was not prolonged in any of the strains. Increased survival was observed when younger mice were given prophylactic therapy. In vivo administration of mel-14, an antibody to a molecule critical to lymphocyte lymph node homing, led to a marked decrease in lymphadenopathy in MRL-lpr/lpr mice.

环磷酰胺是治疗小鼠狼疮的有效药物。 MRL-lpr/lpr 小鼠从 3 个月大起接受皮质类固醇治疗 没有实现显着延长生存期。 其他人报道说，肿瘤坏死因子α（TNF） 缺乏是小鼠狼疮的一个基本缺陷， 替代疗法对于预防疾病非常有效。 我们 已治疗 BXSB 雄性、MRL-lpr/lpr 两性小鼠和 (NZB x NZW)F1小鼠在疾病表现出现后具有TNF。 这种疗法收效甚微。 淋巴结肿大减少 在 MRL-lpr/lpr 小鼠中，但任何小鼠的存活期均未延长 菌株。 当年幼的小鼠被喂食时，观察到存活率增加 给予预防性治疗。 mel-14（一种分子抗体）的体内给药 对淋巴细胞淋巴结归巢至关重要，导致显着减少 MRL-lpr/lpr 小鼠的淋巴结病。