Wednesday, April 2, 2025
4/2/2025
Inflammatory Mechanisms in Post Burn Anemia of Critical Illness - 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.
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