Anemia of Inflammation
Anemia of inflammation, like iron-deficiency anemia, is characterized by low serum iron levels, but it differs from iron-deficiency anemia in that iron stores are preserved in marrow, splenic and hepatic macrophages that recycle senescent erythrocytes. Patients with iron deficiency anemia more often have RBCs with low mean corpuscular volume (MCV) and low mean corpuscular hemoglobin concentration (MCHC) than do patients with anemia of inflammation. Patients with anemia of inflammation often have low serum iron coupled with elevated serum ferritin and hepcidin levels, whereas patients with iron deficiency anemia have low serum iron, low serum ferritin and hepcidin levels.
Iron homeostasis depends on the interplay of hepcidin with ferroportin. Hepcidin is synthesized by hepatocytes and binds to and degrades the iron exporter ferroportin which is present in duodenal enterocytes, splenic macrophages and hepatocytes. When hepcidin levels are high, ferroportin is degraded and iron is retained in cells. When hepcidin is low, ferroportin is stabilized at the cell surface and iron enters into the circulation.
Both increased body iron concentration and inflammation upregulate hepcidin. Hepcidin is transcriptionally activated by proinflammatory cytokines such as IL6. During infections or inflammation, the TLR4-IL6-STAT3 signaling pathway drives hepcidin upregulation and iron retention through ferroportin degradation. This process rapidly induces hypoferremia.
Reference
Silvestri L. The Iron Tale: If it does not kill you, it makes you stronger (and hepcidin helps). HemaSphere 2018;2:1.
