title: Effects of Testosterone on Erythropoiesis in a Female Mouse Model of Anemia of Inflammation.
abstract: The anemia of inflammation is a common problem in inflammatory and autoimmune diseases. We characterized a mouse model of anemia of chronic inflammation induced by repeated injections of low doses of heat-killed Brucella abortus (HKBA), and determined the effects of T administration on erythropoiesis in this model. Female C57BL/6NCrl mice were injected weekly with HKBA for 10 wk. Weekly injections of T or vehicle oil were started 4 wk later. Control mice were injected with saline and vehicle oil in parallel. HKBA-injected mice had significantly lower hemoglobin, hematocrit, mean corpuscular volume, reticulocyte hemoglobin, transferrin saturation (TSAT), and tissue nonheme iron in liver and spleen, enlarged spleen, and up-regulated hepatic expression of inflammatory markers, serum amyloid A1, and TNFα, but down-regulated IL-6, bone morphogenic protein 6, and hepcidin compared with saline controls. HKBA also reduced serum hepcidin and increased serum erythropoietin. Bone marrow erythroid precursors were substantially reduced in HKBA-injected mice. Cotreatment with T increased the percentage of late-stage erythroid precursors in the bone marrow relative to HKBA-injected and saline controls and reversed HKBA-induced suppression of hemoglobin and hematocrit. T also normalized serum erythropoietin, TSAT, and reticulocyte hemoglobin without correcting the expression of the hepatic inflammation markers. Conclusions are that low-dose HKBA induces moderate anemia characterized by chronic inflammation, decreased iron stores, and suppression of erythroid precursors in the bone marrow. T administration reverses HKBA-induced anemia by stimulating erythropoiesis, which is associated with a shift toward accelerated maturation of erythroid precursors in the bone marrow.
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center (W.G., S.B.), and Department of Pathology (P.J.S., M.D.F.), Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Wen
authors.initials: W
authors.lastname: Guo
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center (W.G., S.B.), and Department of Pathology (P.J.S., M.D.F.), Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Schmidt
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center (W.G., S.B.), and Department of Pathology (P.J.S., M.D.F.), Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fleming
authors.affiliation: Research Program in Men's Health: Aging and Metabolism, Boston Claude D. Pepper Older Americans Independence Center (W.G., S.B.), and Department of Pathology (P.J.S., M.D.F.), Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
mesh_terms: D000740:Anemia / Q000378:metabolism*; D000818:Animals; D004920:Erythropoiesis / Q000187:drug effects*; D004921:Erythropoietin / Q000032:analysis; D004958:Estradiol / Q000097:blood; D005260:Female; D006454:Hemoglobins / Q000032:analysis; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*
chemical_list: D006454:Hemoglobins; D004921:Erythropoietin; D013739:Testosterone; D004958:Estradiol