Reder A T, Thapar M, Sapugay A M, Jensen M A
Department of Neurology, University of Chicago, IL 60637.
J Neuroimmunol. 1994 Oct;54(1-2):117-27. doi: 10.1016/0165-5728(94)90238-0.
Experimental allergic encephalomyelitis (EAE) is an autoimmune inflammatory disease of the central nervous system (CNS). It is an animal model of post-infectious encephalomyelitis and multiple sclerosis (MS). Acute EAE is mediated by macrophages and by T helper 1 (Th1) lymphocytes directed against brain antigens. Inflammation in EAE could potentially be modified by prostaglandins (PG) secreted by blood monocytes (Mo) and brain glial cells. PGE elevates cAMP, which inhibits Mo function and selectively blocks secretion of cytokines by Th1 cells. In the present study, we found that a long-acting PGE1 analogue (LAPGE) inhibited clinical and histological EAE. Indomethacin (INDO) also suppressed active EAE. The combination of INDO plus LAPGE inhibited disease further, possibly by allowing LAPGE to function unopposed by immunostimulatory PG. EAE was suppressed when these agents were administered from the time of immunization or from the onset of clinical disease. The combination of INDO plus LAPGE also inhibited delayed-type hypersensitivity (DTH) reactions to myelin basic protein (MBP), and diminished in vitro lymphocyte responses to mitogens and MBP. PGE analogues and modifiers of arachidonate metabolism block autoimmune responses to brain antigens in vitro and in vivo, and may ameliorate inflammatory and autoimmune diseases of the brain and other organs.
实验性变应性脑脊髓炎（EAE）是一种中枢神经系统（CNS）的自身免疫性炎症性疾病。它是感染后脑脊髓炎和多发性硬化症（MS）的动物模型。急性EAE由巨噬细胞和针对脑抗原的辅助性T细胞1（Th1）淋巴细胞介导。EAE中的炎症可能会被血液单核细胞（Mo）和脑胶质细胞分泌的前列腺素（PG）所改变。前列腺素E（PGE）可升高环磷酸腺苷（cAMP），从而抑制Mo功能并选择性地阻断Th1细胞分泌细胞因子。在本研究中，我们发现一种长效PGE1类似物（LAPGE）可抑制EAE的临床和组织学表现。吲哚美辛（INDO）也可抑制活动性EAE。INDO加LAPGE的联合用药可进一步抑制疾病，可能是通过使LAPGE在不受免疫刺激PG拮抗的情况下发挥作用。当从免疫时或临床疾病发作时开始给予这些药物时，EAE得到抑制。INDO加LAPGE的联合用药还可抑制对髓鞘碱性蛋白（MBP）的迟发型超敏反应（DTH），并降低体外淋巴细胞对有丝分裂原和MBP的反应。PGE类似物和花生四烯酸代谢调节剂在体外和体内均可阻断对脑抗原的自身免疫反应，并可能改善脑和其他器官的炎症性和自身免疫性疾病。
