Inflammatory Mechanisms in Post Burn Anemia of Critical Illness

摘要 危重病贫血（ACI）是ICU常见的并发症，在烧伤患者中是主要的并发症， 输血需求的决定因素。不良的医疗结果与过度的 烧伤患者的输血，并迫使采取更保守的输血方案。甚至 随着更保守的输血方法的建立，烧伤患者仍然需要大量的 血对于严重烧伤或创伤的受害者，没有其他方法可以减少输血， 促红细胞生成素（EPO）和铁补充剂不能有效地促进这些患者的红细胞生成。这 是炎症性贫血的特征，例如ACI，其涉及铁限制、红细胞减少 寿命和红细胞生成活性受损。提出这一建议的理由是， 治疗ACI的方法只有在更全面地了解炎症反应的基础上才能实现。 驱动ACI的机制。这项建议的目的是确定有针对性的炎症 可以用来减少烧伤病房和ICU的输血需求的机制。中央 这一建议的假设是烧伤后ACI的发展是受损的EPO信号传导和铁 由G-CSF和IL-6分泌介导的限制，其由炎症信号传导控制。 烧伤。我们建议测试这一假设在三个目标，如果成功将揭示1）炎症 启动烧伤后ACI的网络，2）EBI生态位在烧伤后ACI发病机制中的作用，以及3） 铁限制在烧伤后急性脑梗死发病机制中的作用。圆满完成拟议目标 将确定一个轴的细胞因子，信号传导途径和细胞反应，可以针对批准的 或缓解烧伤后ACI的新兴疗法。

Abstract The anemia of critical illness is (ACI) is a frequent complication in the ICU and in burn patients a primary determinant of transfusion requirements. Poor medical outcomes have been associated with excessive transfusion in burn patients and have compelled the move to more conservative transfusion protocols. Even with the institution of a more conservative approach to transfusion, burn patients still require large quantities of blood. There are no alternatives to reduce transfusion in victims of severe burn or trauma because erythropoietin (EPO) and iron supplementation do not effectively promote erythropoiesis in these patients. This is characteristic of an inflammatory anemia such as ACI that involves iron restriction, reduced erythrocyte lifespan and impairment of erythropoietic activity. The rationale for this proposal is that development of therapeutic approaches to treat ACI can only be realized with a more complete understanding of inflammatory mechanisms that drive ACI. The objective of this proposal is to identify the targetable inflammatory mechanisms that can be exploited to reduce transfusion requirements in the burn unit and ICU. The central hypothesis of this proposal is that post burn ACI develops as a result of impaired EPO signaling and iron restriction that are mediated by G-CSF and IL-6 secretion that is controlled by inflammatory signaling in the burn wound. We propose test this hypothesis in three aims that if successful will reveal 1) the inflammatory networks that initiate post burn ACI, 2) the role of the EBI niche in the pathogenesis of post burn ACI, and 3) the role of iron restriction in the pathogenesis of post burn ACI. Successful completion of the proposed aims will identify an axis of cytokines, signaling pathways, and cellular responses that can be targeted with approved or emerging therapeutics to alleviate post burn ACI.