Physiology and Inflammation Driven Pathophysiology of Iron Homeostasis—Mechanistic Insights into Anemia of Inflammation and Its Treatment

Abstract

Anemia is very common in patients with inflammatory disorders. Its prevalence is associated with severity of the underlying disease, and it negatively affects quality of life and cardio-vascular performance of patients. Anemia of inflammation (AI) is caused by disturbances of iron metabolism resulting in iron retention within macrophages, a reduced erythrocyte half-life, and cytokine mediated inhibition of erythropoietin function and erythroid progenitor cell differentiation. AI is mostly mild to moderate, normochromic and normocytic, and characterized by low circulating iron, but normal and increased levels of the storage protein ferritin and the iron hormone hepcidin. The primary therapeutic approach for AI is treatment of the underlying inflammatory disease which mostly results in normalization of hemoglobin levels over time unless other pathologies such as vitamin deficiencies, true iron deficiency on the basis of bleeding episodes, or renal insufficiency are present. If the underlying disease and/or anemia are not resolved, iron supplementation therapy and/or treatment with erythropoietin stimulating agents may be considered whereas blood transfusions are an emergency treatment for life-threatening anemia. New treatments with hepcidin-modifying strategies and stabilizers of hypoxia inducible factors emerge but their therapeutic efficacy for treatment of AI in ill patients needs to be evaluated in clinical trials.