The role of iron in chronic inflammatory diseases: from mechanisms to treatment options in anemia of inflammation

Abstract

Anemia of Inflammation (AI) is a highly prevalent comorbidity in patients affected by chronic inflammatory disorders, such as Chronic Kidney Disease, Inflammatory Bowel Disease or Cancer that negatively impacts on disease outcome and quality of life. The pathophysiology of AI is multifactorial, whereby inflammatory hypoferremia and iron-restricted erythropoiesis play a major role in the context of disease-specific factors. Here we review the recent progress in our understanding of the molecular mechanisms contributing to iron dysregulation in AI, the impact of hypoferremia and anemia on the course of the underlying disease as well as (novel) therapeutic strategies applied to treat AI.

ApoE Mimetic Peptides to Improve the Vicious Cycle of Malnutrition and Enteric Infections by Targeting the Intestinal and Blood-Brain Barriers

“…EED-related persistent low-grade systemic inflammation may also be a concern for growing children since it may cause anemia of inflammation or anemia of chronic diseases [52,53]. Such conditions may be aggravated by the exploitation of enteric parasites [54,55].…”

Anemia of chronic diseases: a verdict or a protective reaction of the body?

“…Однако основной источник железа для макрофагов -стареющие эритроциты. Цитокины, радикалы, полученные из очага воспаления, и факторы комплемента повреждают эритроциты и способствуют эритрофагоцитозу путём стимуляции рецепторов, распознающих стареющие эритроциты [30].…”

Accelerating action to reduce anemia: Review of causes and risk factors and related data needs

“…Proinflammatory cytokines increase the synthesis of an iron-regulating hormone, hepcidin, which causes the sequestration of iron as ferritin, thereby blocking iron transfer to erythrocyte precursor cells in the bone marrow and resulting in decreased erythropoiesis as well as decreased erythrocyte survival. [20][21][22][23] The exact pathological mechanisms depend on the underlying infection or disease causing the anemia. 23 Soil-transmitted helminths, including hookworm (Necator americanus and Ancylostoma duodenale), Trichuris trichiura, and Ascaris lumbricoides, parasitize the gastrointestinal tract causing blood loss, which in turn can result in the loss of iron and the development of anemia.…”

“…[20][21][22][23] The exact pathological mechanisms depend on the underlying infection or disease causing the anemia. 23 Soil-transmitted helminths, including hookworm (Necator americanus and Ancylostoma duodenale), Trichuris trichiura, and Ascaris lumbricoides, parasitize the gastrointestinal tract causing blood loss, which in turn can result in the loss of iron and the development of anemia. 24 Globally, about 1.5 billion people are estimated to be infected with soil-transmitted helminths, with the highest infection rates in areas with poor sanitation in tropical and subtropical regions of sub-Saharan Africa, the Americas, China, and East Asia.…”

“…Inflammation and chronic disease can also lead to anemia known as anemia of inflammation, which is immune‐driven. Proinflammatory cytokines increase the synthesis of an iron‐regulating hormone, hepcidin, which causes the sequestration of iron as ferritin, thereby blocking iron transfer to erythrocyte precursor cells in the bone marrow and resulting in decreased erythropoiesis as well as decreased erythrocyte survival 20–23 . The exact pathological mechanisms depend on the underlying infection or disease causing the anemia 23 .…”