de Kossodo S, Grau G E
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas.
Stem Cells. 1993 Jan;11(1):41-8. doi: 10.1002/stem.5530110108.
Cerebral malaria (CM) is the most common cause of death in severe malaria; more than two million children die of CM annually. Although the mechanisms of this neurologic complication remain poorly understood, studies in an experimental model of CM suggest that a natural body protein seems to be a major cause of this deadliest complication of malaria, a finding that could point towards new methods of treatment. We have explored the pathogenesis of CM with particular attention to the possible relationship between susceptibility or resistance to CM and cytokine expression and secretion patterns. We found that CM is associated with an increased expression of tumor necrosis factor (TNF) and interferon (IFN)-gamma and a reduced expression of interleukin-4 (IL-4) and transforming growth factor (TGF)-beta. The data obtained are consistent with a predominantly Th1 response in mice developing the cerebral complications of malaria. The overexpression of TNF in brain was also correlated with the augmented expression of adhesion molecules involved in the sequestration of leukocytes in brain vessels, a distinctive feature of CM. These observations were seen in relation to the immune status of man, in which, akin to the mouse model, a predominant Th1 response and upregulation of adhesion molecules in brain endothelium appear to be associated with susceptibility to the neurological complications of CM.
脑型疟疾（CM）是重症疟疾最常见的死亡原因；每年有超过200万儿童死于脑型疟疾。尽管这种神经并发症的机制仍知之甚少，但在脑型疟疾实验模型中的研究表明，一种天然人体蛋白似乎是疟疾这种最致命并发症的主要原因，这一发现可能指向新的治疗方法。我们探讨了脑型疟疾的发病机制，特别关注对脑型疟疾的易感性或抗性与细胞因子表达及分泌模式之间的可能关系。我们发现，脑型疟疾与肿瘤坏死因子（TNF）和干扰素（IFN）-γ的表达增加以及白细胞介素-4（IL-4）和转化生长因子（TGF）-β的表达降低有关。所获得的数据与发生疟疾脑部并发症的小鼠中主要为Th1反应一致。脑中TNF的过度表达也与参与白细胞在脑血管中滞留的黏附分子表达增加相关，这是脑型疟疾的一个显著特征。在人类免疫状态方面也观察到了这些现象，与小鼠模型类似，人类中主要的Th1反应以及脑内皮中黏附分子的上调似乎与对脑型疟疾神经并发症的易感性有关。
