Cytokines and Chemokines in Cerebral Malaria Pathogenesis.
Cytokines and Chemokines in Cerebral Malaria Pathogenesis.
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DOI：
10.3389/fcimb.2017.00324
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发表时间：
2017
影响因子：
5.7
通讯作者：
Matuschewski K
中科院分区：
文献类型：
--
作者：
Dunst J;Kamena F;Matuschewski K
脑型疟疾是疟疾相关死亡的主要原因之一，目前缺乏有效的预防性治疗策略。参与脑型疟疾发展的中心病理生理过程包括对疟原虫感染的促炎和抗炎反应的不平衡、内皮细胞活化和血脑屏障完整性的丧失。然而，事件的顺序，启动这些病理生理过程，以及其复杂的相互作用脑型疟疾的发展的贡献仍然不完全清楚。几种细胞因子和趋化因子已反复与脑型疟疾的严重程度。这些炎症介质水平的增加可以解释脑型疟疾期间存在的脑微血管中白细胞的隔离，从而有助于局部炎症的放大和促进脑型疟疾的发病机制。在此，我们强调了目前的知识，细胞因子和趋化因子的脑型疟疾的发病机制，特别强调其在内皮细胞活化和白细胞招募的作用，以及它们的意义的进展，血脑屏障通透性和神经炎症，在人类脑型疟疾和小鼠实验性脑型疟疾模型。对这些过程的更好的分子理解可以为辅助治疗的循证开发和疾病进展诊断标志物的定义提供基础。
Cerebral malaria is among the major causes of malaria-associated mortality and effective adjunctive therapeutic strategies are currently lacking. Central pathophysiological processes involved in the development of cerebral malaria include an imbalance of pro- and anti-inflammatory responses to Plasmodium infection, endothelial cell activation, and loss of blood-brain barrier integrity. However, the sequence of events, which initiates these pathophysiological processes as well as the contribution of their complex interplay to the development of cerebral malaria remain incompletely understood. Several cytokines and chemokines have repeatedly been associated with cerebral malaria severity. Increased levels of these inflammatory mediators could account for the sequestration of leukocytes in the cerebral microvasculature present during cerebral malaria, thereby contributing to an amplification of local inflammation and promoting cerebral malaria pathogenesis. Herein, we highlight the current knowledge on the contribution of cytokines and chemokines to the pathogenesis of cerebral malaria with particular emphasis on their roles in endothelial activation and leukocyte recruitment, as well as their implication in the progression to blood-brain barrier permeability and neuroinflammation, in both human cerebral malaria and in the murine experimental cerebral malaria model. A better molecular understanding of these processes could provide the basis for evidence-based development of adjunct therapies and the definition of diagnostic markers of disease progression.