McDevitt Michael A, Xie Jianlin, Gordeuk Victor, Bucala Richard
Department of Medicine and Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.
Curr Hematol Rep. 2004 Mar;3(2):97-106.
Death from malaria occurs from the complications of the infection: cerebral manifestations leading to coma and a severe and refractory anemia leading to hypoxia and cardiac decompensation. Several mechanisms have been identified to play a role in the pathogenesis of malarial anemia, such as erythrocyte lysis and phagocytosis, and sequestration of parasitized red blood cells, but recent data indicate that these mechanisms (singly or in combination) do not adequately explain the severity of this anemia. By contrast, hematologic studies have shown that bone marrow suppression and ineffective erythropoiesis contribute importantly to the severe anemia of malaria infection. The host mechanisms responsible for suppression of erythropoiesis may involve an excessive or sustained innate immune response or a pathologic skewing of the T-cell differentiation response with the attendant production of certain proinflammatory cytokines. Experimental data also indicate that severe malarial anemia is associated with the immunologic expression of a circulating inhibitor of erythropoiesis that functionally antagonizes the action of erythropoietin. We review the clinical and experimental basis for these concepts and discuss ongoing experimental and genetic studies aimed at unraveling the molecular basis of this malaria-induced bone marrow suppression.
脑部表现导致昏迷，严重且难以治愈的贫血导致缺氧和心脏代偿失调。已确定多种机制在疟疾贫血的发病过程中起作用，如红细胞溶解和吞噬作用，以及被寄生红细胞的滞留，但最近的数据表明，这些机制（单独或联合）并不能充分解释这种贫血的严重程度。相比之下，血液学研究表明，骨髓抑制和无效造血对疟疾感染导致的严重贫血起重要作用。负责抑制造血的宿主机制可能涉及过度或持续的固有免疫反应，或T细胞分化反应的病理性偏差以及随之产生的某些促炎细胞因子。实验数据还表明，严重疟疾贫血与一种循环造血抑制因子的免疫表达有关，该因子在功能上拮抗促红细胞生成素的作用。我们回顾了这些概念的临床和实验依据，并讨论了旨在阐明这种疟疾诱导的骨髓抑制分子基础的正在进行的实验和遗传学研究。
