Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine produced by immune cells; it can play a protective or deleterious role in response to pathogens. The intracellular malaria parasite secretes a similar protein, PMIF. The present paper is concerned with severe malarial anemia (SMA), where MIF suppresses the recruitment of red blood cells (RBCs) from the spleen and the bone marrow. This suppression results in a decrease of the hemoglobin (Hb) in the blood to a dangerous level. Indeed, SMA is responsible for the majority of death-related malaria cases. Artesunate is the first line of treatment of SMA; it accelerates the death of infected RBCs (iRBCs), thereby decreasing parasitemia. However, artesunate does not increase the level of Hb, and, in some cases, post-artesunate hemolytic anemia requires blood transfusion. In order to avoid this situation, we explore combining artesunate with another drug so that the Hb level is increased to healthy levels while parasitemia is still controlled. In this paper we show, by a mathematical model, that increasing the Hb levels while controlling parasitemia in malarial anemia can be done with the experimental drug Epoxyazadiradione (Epoxy) in combination with artesunate. Epoxy acts as MIF inhibitor and thus has the potential to increase the Hb level. Simulations of the model show that the two drugs compliment each other: while artesunate is primarily responsible for decreasing parasitemia, Epoxy is primarily responsible for increasing the hemoglobin level.

中文翻译：

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在控制寄生虫血症的同时，在严重疟疾贫血中增加血红蛋白水平：一种数学模型。

巨噬细胞迁移抑制因子（MIF）是由免疫细胞产生的多效性细胞因子。它可以对病原体起保护作用或有害作用。细胞内疟原虫会分泌类似的蛋白质PMIF。本文涉及严重的疟疾贫血（SMA），其中MIF抑制了脾脏和骨髓中红细胞（RBC）的募集。这种抑制导致血液中的血红蛋白（Hb）降至危险水平。确实，SMA导致​​了大多数与死亡有关的疟疾病例。青蒿琥酯是SMA治疗的第一线。它加速了受感染的红细胞（iRBC）的死亡，从而降低了寄生虫病。但是，青蒿琥酯并不会增加Hb的水平，在某些情况下，青蒿琥酯后溶血性贫血需要输血。为了避免这种情况，我们尝试将青蒿琥酯与另一种药物结合使用，以使Hb水平增加到健康水平，同时仍控制寄生虫血症。在本文中，我们通过数学模型表明，通过结合实验性药物Epoxyazadiradione（Epoxy）和青蒿琥酯来控制疟疾贫血中的寄生虫病，同时提高Hb水平。环氧树脂充当MIF抑制剂，因此有可能增加Hb水平。该模型的仿真表明，两种药物互为补充：青蒿琥酯主要负责降低寄生虫病，而环氧树脂主要负责提高血红蛋白水平。在本文中，我们通过数学模型表明，通过结合实验性药物Epoxyazadiradione（Epoxy）和青蒿琥酯来控制疟疾贫血中的寄生虫病，同时提高Hb水平。环氧树脂充当MIF抑制剂，因此有可能增加Hb水平。该模型的仿真表明，两种药物互为补充：青蒿琥酯主要负责降低寄生虫病，而环氧树脂主要负责提高血红蛋白水平。在本文中，我们通过数学模型表明，通过结合实验性药物Epoxyazadiradione（Epoxy）和青蒿琥酯来控制疟疾贫血中的寄生虫病，同时提高Hb水平。环氧树脂充当MIF抑制剂，因此有可能增加Hb水平。该模型的仿真表明，两种药物互为补充：青蒿琥酯主要负责减少寄生虫病，而环氧树脂主要负责增加血红蛋白水平。