title: HMGB1 Mediates Anemia of Inflammation in Murine Sepsis Survivors.
abstract: Patients surviving sepsis develop anemia, but the molecular mechanism is unknown. Here we observed that mice surviving polymicrobial gram-negative sepsis develop hypochromic, microcytic anemia with reticulocytosis. The bone marrow of sepsis survivors accumulates polychromatophilic and orthochromatic erythroblasts. Compensatory extramedullary erythropoiesis in the spleen is defective during terminal differentiation. Circulating tumor necrosis factor (TNF) and interleukin (IL)-6 are elevated for 5 d after the onset of sepsis, and serum high-mobility group box 1 (HMGB1) levels are increased from d 7 until at least d 28. Administration of recombinant HMGB1 to healthy mice mediates anemia with extramedullary erythropoiesis and significantly elevated reticulocyte counts. Moreover, administration of anti-HMGB1 monoclonal antibodies after sepsis significantly ameliorates the development of anemia (hematocrit 48.5 ± 9.0% versus 37.4 ± 6.1%, p < 0.01; hemoglobin 14.0 ± 1.7 versus 11.7 ± 1.2 g/dL, p < 0.01). Together, these results indicate that HMGB1 mediates anemia by interfering with erythropoiesis, suggesting a potential therapeutic strategy for anemia in sepsis.
authors.affiliation: Elmezzi Graduate School of Molecular Medicine, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.|Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Sergio I
authors.initials: SI
authors.lastname: Valdés-Ferrer
authors.affiliation: Laboratory of Developmental Erythropoiesis, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Julien
authors.initials: J
authors.lastname: Papoin
authors.affiliation: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Meghan E
authors.initials: ME
authors.lastname: Dancho
authors.affiliation: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Peder S
authors.initials: PS
authors.lastname: Olofsson
authors.affiliation: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.affiliation: Laboratory of Developmental Erythropoiesis, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Lipton
authors.affiliation: Laboratory of Hematopoiesis, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Patricia
authors.initials: P
authors.lastname: Avancena
authors.affiliation: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Laboratory of Hematopoiesis, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Yong-Rui
authors.initials: YR
authors.lastname: Zou
authors.affiliation: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Sangeeta S
authors.initials: SS
authors.lastname: Chavan
authors.affiliation: Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Volpe
authors.affiliation: Children's Hospital of Philadelphia, Department of Pediatrics, Division of Hematology, Philadelphia, Pennsylvania, United States of America.
authors.forename: Sara
authors.initials: S
authors.lastname: Gardenghi
authors.affiliation: Children's Hospital of Philadelphia, Department of Pediatrics, Division of Hematology, Philadelphia, Pennsylvania, United States of America.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rivella
authors.affiliation: Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
authors.affiliation: Departments of Women's and Children's Health, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Andersson
authors.affiliation: Elmezzi Graduate School of Molecular Medicine, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.|Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Bettie M
authors.initials: BM
authors.lastname: Steinberg
authors.affiliation: Laboratory of Developmental Erythropoiesis, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Lionel
authors.initials: L
authors.lastname: Blanc
authors.affiliation: Elmezzi Graduate School of Molecular Medicine, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.|Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Tracey