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: Wen Guo, Paul J Schmidt, Mark D Fleming, Shalender Bhasin
• Journal: Endocrinology (Endocrinology) Vol. 157 Issue 7 Pg. 2937-46 (07 2016) ISSN: 1945-7170 [Electronic] United States
• PMID: 27074351 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)

Chemical References

• Hemoglobins
• Erythropoietin
• Testosterone
• Estradiol

Topics

• Anemia (metabolism)
• Animals
• Erythropoiesis (drug effects)
• Erythropoietin (analysis)
• Estradiol (blood)
• Female
• Hemoglobins (analysis)
• Inflammation (metabolism)
• Mice
• Mice, Inbred C57BL
• Testosterone (blood, pharmacology)