Hyperferritinemia and inflammation

Abstract

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.

Reply to: Comment on: CD163 as a valuable diagnostic and prognostic biomarker of sepsis‐associated hemophagocytic lymphohistiocytosis in critically ill children. A call for HLA‐DR in HLH

“…7 High ferritin levels can be triggered by a variety of clinical and pathophysiological mechanisms that are similar to HLH. 8 In our study, elevated ferritin levels (>1554 g/L) at 7 days after treatment of sepsis displayed considerable power for differentiating SAHS from sepsis. The cutoff value of ferritin was lower than the established level of 10 000 g/L.…”

“…Otrock and colleagues proved that a serum ferritin level >10 000 μg/L is not specific for HLH in either 583 adult patients or 45 children . High ferritin levels can be triggered by a variety of clinical and pathophysiological mechanisms that are similar to HLH . In our study, elevated ferritin levels (>1554 μg/L) at 7 days after treatment of sepsis displayed considerable power for differentiating SAHS from sepsis.…”

Profiling of the Risk Factors and Designing of a Model to Identify Ischemic Stroke in Patients with Non-Hodgkin Lymphoma: A Multicenter Retrospective Study

“…More importantly, during the course of the study, we also found how SF was an independent risk factor for NHLAIS. SF (an iron storage protein) is related to inflammation and closely linked to a hypercoagulable state in patients with cancer [25][26][27]. Although the detailed mechanism of SF in a hypercoagulable state remains unclear, we speculated that elevated SF may promote hypercoagulability due to severe inflammatory response, leading to ischemic stroke in NHL patients.…”

Association between serum ferritin and the severity of drug eruptions

“…Ferritin is an iron storage protein influenced by the intracellular iron concentrations. It is also an acute‐phase protein, which is increased in the setting of inflammation, even exceeding 10 000 ng/mL in septic shock and infectious diseases with macrophage activation . Increased ferritin level is also observed in alcoholism, cytolysis (including hepatic and muscle cytolysis), metabolic syndrome, juvenile idiopathic arthritis, and adult‐onset Still's disease .…”

“…activation. [7][8][9] Increased ferritin level is also observed in alcoholism, cytolysis (including hepatic and muscle cytolysis), metabolic syndrome, juvenile idiopathic arthritis, and adult-onset Still's disease. [10][11][12] One study revealed that ferritin could be a useful early prognostic factor in DRESS.…”