Hyperferritinemia and inflammation

• Published in: International immunology Vol. 29; no. 9; pp. 401 - 409
• Main Authors: Kernan, Kate F, Carcillo, Joseph A
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-11-2017
• Subjects: Acute-Phase Reaction; Animals; Cataract - congenital; Ferritins - metabolism; Hemochromatosis; Humans; Immunity, Innate; Immunomodulation; Inflammation; Invited Reviews; Iron - metabolism; Iron Metabolism Disorders - congenital; hemophagocytosis; hemophagocytic lymphohistiocytosis; iron; ferritin; macrophage activation
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxx031

Understanding of ferritin biology has traditionally centered on its role in iron storage and homeostasis, with low ferritin levels indicative of deficiency and high levels indicative of primary or secondary hemochromatosis. However, further work has shown that iron, redox biology and inflammation are inexorably linked. During infection, increased ferritin levels represent an important host defense mechanism that deprives bacterial growth of iron and protects immune cell function. It may also be protective, limiting the production of free radicals and mediating immunomodulation. Additionally, hyperferritinemia is a key acute-phase reactants, used by clinicians as an indication for therapeutic intervention, aimed at controlling inflammation in high-risk patients. One school of thought maintains that hyperferritinemia is an 'innocent bystander' biomarker of uncontrolled inflammation that can be used to gauge effectiveness of intervention. Other schools of thought maintain that ferritin induction could be a protective negative regulatory loop. Others maintain that ferritin is a key mediator of immune dysregulation, especially in extreme hyperferritinemia, via direct immune-suppressive and pro-inflammatory effects. There is a clear need for further investigation of the role of ferritin in uncontrolled inflammatory conditions both as a biomarker and mediator of disease because its occurrence identifies patients with high mortality risk and its resolution predicts their improved survival.