Title |
HMGB1 Mediates Anemia of Inflammation in Murine Sepsis Survivors
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Published in |
Molecular Medicine, December 2015
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DOI | 10.2119/molmed.2015.00243 |
Pubmed ID | |
Authors |
Sergio I. Valdés-Ferrer, Julien Papoin, Meghan E. Dancho, Peder S. Olofsson, Jianhua Li, Jeffrey M. Lipton, Patricia Avancena, Huan Yang, Yong-Rui Zou, Sangeeta S. Chavan, Bruce T. Volpe, Sara Gardenghi, Stefano Rivella, Betty Diamond, Ulf Andersson, Bettie M. Steinberg, Lionel Blanc, Kevin J. Tracey |
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 TNF and IL-6 are elevated for five days after the onset of sepsis, and serum HMGB1 levels are increased from day seven until at least day 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±1.7g/dL versus 11.7±1.2g/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. |
X Demographics
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Unknown | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 35 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 6 | 17% |
Professor | 3 | 9% |
Professor > Associate Professor | 3 | 9% |
Student > Ph. D. Student | 3 | 9% |
Student > Bachelor | 2 | 6% |
Other | 3 | 9% |
Unknown | 15 | 43% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 6 | 17% |
Immunology and Microbiology | 5 | 14% |
Agricultural and Biological Sciences | 3 | 9% |
Biochemistry, Genetics and Molecular Biology | 3 | 9% |
Unspecified | 1 | 3% |
Other | 2 | 6% |
Unknown | 15 | 43% |