Date of Award
Fall 2013
Document Type
Thesis
Abstract
Anemia is a ubiquitous finding in patients with sepsis and chronic inflammatory disorders. High mobility group box 1 (HMGB1) is a DNA-binding nuclear protein with extracellular cytokine-like chemotactic and inflammatory activity. Circulating HMGB1 is persistently elevated during sepsis. Although HMGB1 is sufficient to induce sepsis, its role in anemia of critical illness has not been previously studied. Here, using a murine model of severe sepsis induced by cecal ligation and puncture (CLP), mice developed anemia three days post sepsis. Analysis of terminal erythroid differentiation demonstrated an increase in all erythroid progenitors, from proerythroblast to orthochromatic erythroblast, contrasting with a decrease of reticulocyte and RBC populations. Persistent administration of rHMGB1 to healthy mice was sufficient to induce anemia and splenomegaly. rHMGB1 induced stress erythropoiesis, but not an expansion of mature RBCs.
Administration of anti-HMGB1 to mice surviving CLP rescued them form the anemic phenotype. These results highlight a novel and critical role for HMGB1 as key modulator of erythropoiesis in sepsis survivors.
Recommended Citation
Valdés-Ferrer, Sergio Iván MD, "HMGB1 is a key mediator of sustained inflammation in sepsis survivors." (2013). Elmezzi Graduate School of Molecular Medicine Theses. 18.
https://academicworks.medicine.hofstra.edu/elmezzi_theses/18