TUMOR-NECROSIS-FACTOR (CACHECTIN) AS AN ESSENTIAL MEDIATOR IN MURINE CEREBRAL MALARIA
TUMOR-NECROSIS-FACTOR (CACHECTIN) AS AN ESSENTIAL MEDIATOR IN MURINE CEREBRAL MALARIA
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DOI：
10.1126/science.3306918
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发表时间：
1987-09-04
期刊：
影响因子：
56.9
通讯作者：
VASSALLI, P
中科院分区：
文献类型：
--
作者：
GRAU, GE;FAJARDO, LF;VASSALLI, P
肿瘤坏死因子或恶病素(TNF-α)是一种具有广泛生物活性的蛋白质，主要由巨噬细胞产生，并且在炎症过程中可能很重要。 TNF-α的作用。在小鼠模型中研究了脑型疟疾的发病机制。大多数感染伯氏疟原虫的 CBA 小鼠在第 6 至 14 天之间死亡，并伴有与寄生虫血症水平无关的急性神经系统表现，而其他一些品系的小鼠患有相同严重程度的疟疾，在 3 至 4 周后死亡，但没有神经系统表现。血清TNF-α的活性。在患有脑型疟疾的 CBA/Ca 小鼠中，该值显着增加，但在没有出现这种并发症的伯氏疟原虫感染的小鼠中则没有显着增加。注射 1 次兔 TNF-α 抗体。在第 4 或 7 天，完全保护受感染的小鼠免受脑型疟疾的侵害，而不会改变寄生虫血症，而来自正常兔子的免疫球蛋白则没有效果。在患有脑型疟疾的小鼠中，脑血管显示聚集的巨噬细胞的聚集，通常含有受感染的红细胞；在用TNF-α抗体治疗的小鼠中没有观察到这种病变。或在未经治疗的没有脑型疟疾的小鼠中。这些发现表明 TNF-α。在此小鼠模型中，脑型疟疾的发病机制具有重要作用，表明巨噬细胞的局部积累和激活可能导致中枢神经系统的病变占主导地位。
Tumor necrosis factor, or cachectin (TNF-.alpha.), a protein with a wide range of biological activities, is produced mainly by macrophages and may be important in inflammatory processes. The role of TNF-.alpha. in the pathogenesis of cerebral malaria was investigated in a murine model. Most CBA mice infected with Plasmodium berghei anka die between days 6 and 14 with acute neurological manifestations unrelated to the level of parasitemia, whereas mice of some other strains have malaria of the same severity that ends in death after 3 to 4 weeks without neurological manifestations. The activity of serum TNF-.alpha. was considerably increased in CBA/Ca mice with cerebral malaria but not in Plasmodium berghei-infected mice that did not develop this complication. One injection of rabbit antibody to TNF-.alpha. on day 4 or 7 fully protected infected mice from cerebral malaria without modifying the parasitemia, whereas immunoglobulins from normal rabbit had no effect. In mice with cerebral malaria, the cerebral vessels showed focal accumulations of packed macrophages often containing infected erythrocytes; this lesion was not seen in mice treated with antibody to TNF-.alpha. or in untreated mice without cerebral malaria. These findings indicate that TNF-.alpha. has an important role in the pathogenesis of cerebral malaria in this murine model and suggest that local accumulation and activation of macrophages may lead to the predominance of lesions in the central nervous system.