[The pathogenesis of anemia in inflammation]

Inflammation is a physiological process that primarily occurs as a way to help protect the host against tissue damage and invasion by pathogens. During inflammation, erythropoiesis is suppressed and, if it lasts, anemia develops. The mechanisms underlying this are complex and not fully understood, but various cytokines, such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1β (IL-1β), and IL-6, are involved. TNF-α upregulates PU.1, which is a crucial transcription factor in granulocytic differentiation, and downregulates GATA-1, a master transcription factor for erythroid differentiation, in hematopoietic stem cells. TNF-α and IL-1β suppress erythropoietin production in the kidney, whereas IFN-γ downregulates the expression of erythropoietin receptors in erythroid precursor cells. Moreover, IL-6 upregulates the production of hepcidin, the master regulator of systemic iron metabolism, in the liver. Hepcidin reduces the iron available for erythropoiesis by downregulating the rate of iron release from macrophages. Activated macrophages may also contribute to the development of anemia by shortening the erythrocyte lifespan. Proper management of the underlining conditions is necessary in treating anemia associated with inflammation. Erythropoiesis-stimulating agents may be administered to patients with chronic kidney disease, whereas anti-IL-6 agents may be beneficial for anemic patients with rheumatoid arthritis and idiopathic multicentric Castleman disease.