Anemia of Inflammation

Anemia of chronic disease (ACD), also known as anemia of inflammation (AI), is a common complication of infections, autoimmune diseases, malignancies, chronic kidney disease, and other inflammatory diseases, and is second only to iron deficiency anemia (IDA). Although the pathophysiological mechanisms of AI are not fully elucidated, the release of inflammatory cytokines leading to increased synthesis and secretion of hepcidin, abnormalities in body iron homeostasis, and consequently iron-restricted erythropoiesis are the most important reasons for its occurrence. The typical iron metabolism is characterized by elevated serum hepcidin levels, decreased serum iron concentration and transferrin saturation, decreased iron absorption in the gastrointestinal tract and iron retention in the mononuclear macrophage system.

Iron Metabolism Abnormalities in ACD

Imbalance of iron metabolism is a common cause of certain clinical disorders and a major cause of ACD. Iron regulation is affected by hypoxia, inflammation, infection and hereditary or nutritional iron deficiency, and responds to abnormal erythropoiesis. Under normal physiological conditions, the body strictly controls the dynamic balance of iron through synergistic effects at the systemic and cellular levels; when the body is in a pathological state such as chronic inflammation or tumor, iron-regulated synthesis increases, and imbalance of iron metabolism causes hypoferritinemia and can lead to the development of ACD.

• Iron Restriction
  In animal models of ACD and in patients with inflammatory diseases, elevated hepcidin levels are associated with low iron transporter protein expression on duodenal enterocytes and macrophages, as well as impaired dietary iron absorption and iron retention in macrophages, leading to reduced erythropoiesis by iron transport.

Pathogenesis of ACD

Chronic inflammatory anemia is dominated by disorders of iron metabolism and abnormalities in iron incorporation into red lineage precursor cells. Increased production of iron-regulated factors induced by inflammatory factors is the key to chronic inflammatory anemia. If the levels of inflammatory cytokines IL-1, IL-6, TNF-a, and BMP are elevated in the body, the inflammatory cytokines cause increased ferroregulin transcription and elevated serum levels through different signaling pathways. Increased levels of ferro regulators close iron export channels, leading to recirculating iron blockage by monocytes and reduced iron uptake in the gastrointestinal tract. Thus, inflammatory anemia is not a deficiency of iron but a problem of iron utilization and iron metabolism.

Schematic diagram of the mechanism of iron-regulated hormone regulation in ACD ^[1].

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Systemic changes in iron utilization, erythropoiesis, and erythrocyte survival characteristics lead to inflammatory anemia. Protheragen, with its research experience in the field of physiological metabolism, helps clients to conduct in-depth studies on the physiological mechanisms of ACD, providing new therapeutic ideas for the prevention and treatment of the disease. If you are interested in the services we offer, please contact us for more information.