Kremsner P G, Grundmann H, Neifer S, Sliwa K, Sahlmüller G, Hegenscheid B, Bienzle U
Landesinstitut für Tropenmedizin Berlin, Germany.
J Infect Dis. 1991 Sep;164(3):605-8. doi: 10.1093/infdis/164.3.605.
Pentoxifylline, a widely used methylxanthine, was tested for its capacity to prevent cerebral malaria (CM) in Plasmodium berghei ANKA-infected CBA/Ca mice. Nine of 12 control mice developed neurologic signs and died from CM approximately 2 weeks after infection. All 12 mice treated with daily intraperitoneal pentoxifylline (1 mg) for 10 days after infection did not develop CM. All surviving mice developed high parasitemia and severe anemia and died 2 weeks later without neurologic signs. In pentoxifylline-treated mice, serum tumor necrosis factor (TNF) bioactivity was nondetectable, whereas control mice had high TNF levels on day 6 after infection. These findings were supported by in vitro investigations of malaria antigen-induced TNF synthesis. Northern blot analysis of TNF mRNA from stimulated macrophages showed that pentoxifylline inhibited TNF expression at the transcription level, and TNF bioactivity in supernatants was strongly depressed. These findings make pentoxifylline a potential candidate for study as a supportive agent in human CM.
己酮可可碱是一种广泛使用的甲基黄嘌呤，在感染伯氏疟原虫ANKA的CBA/Ca小鼠中测试了其预防脑型疟疾（CM）的能力。12只对照小鼠中有9只在感染后约2周出现神经症状并死于脑型疟疾。感染后每天腹腔注射己酮可可碱（1毫克），持续10天，所有12只小鼠均未发生脑型疟疾。所有存活小鼠均出现高寄生虫血症和严重贫血，并在2周后无神经症状死亡。在己酮可可碱治疗的小鼠中，未检测到血清肿瘤坏死因子（TNF）生物活性，而对照小鼠在感染后第6天TNF水平较高。这些发现得到了疟疾抗原诱导的TNF合成的体外研究的支持。对刺激巨噬细胞的TNF mRNA进行Northern印迹分析表明，己酮可可碱在转录水平抑制TNF表达，上清液中的TNF生物活性强烈降低。这些发现使己酮可可碱成为作为人类脑型疟疾支持药物研究的潜在候选者。
