Is ferritin an inflammatory marker?

From the Guidelines

Ferritin itself is not inflammatory, but it is an acute phase reactant that increases during inflammation. Ferritin is primarily an iron storage protein that helps regulate iron levels in the body. During inflammatory states, the body increases ferritin production as part of the immune response, even when iron stores are normal or low. This is why elevated ferritin levels can be seen in various inflammatory conditions such as infections, autoimmune disorders, and chronic diseases, not just in cases of iron overload. This phenomenon, known as the acute phase response, can make ferritin levels less reliable as a sole indicator of iron status during inflammation.

When evaluating ferritin levels in a clinical setting, it's essential to consider other inflammatory markers like C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) to properly interpret whether high ferritin reflects true iron excess or is simply a response to inflammation, as noted in the most recent guidelines 1. The body increases ferritin during inflammation partly as a protective mechanism to sequester iron away from pathogens that require iron for growth.

Some key points to consider when interpreting ferritin levels include:

• In patients without clinical, endoscopic, or biochemical evidence of active disease, serum ferritin <30 mg/L is an appropriate criterion for the diagnosis of iron deficiency anemia 1.
• In the presence of inflammation, a serum ferritin up to 100 mg/L may still be consistent with iron deficiency 1.
• In the presence of biochemical or clinical evidence of inflammation, the diagnostic criteria for anemia of chronic disease are a serum ferritin >100 mg/L and transferrin saturation <20% 1.
• If the serum ferritin level is between 30 and 100 mg/L, a combination of true iron deficiency and anemia of chronic disease is likely 1.

Overall, ferritin levels should be interpreted with caution in the context of inflammation, and other markers of iron status and inflammation should be considered to accurately diagnose and manage iron deficiency anemia, as recommended by the most recent and highest quality study 1.

From the Research

Ferritin and Inflammation

• Ferritin is associated with low-grade inflammation, as increased plasma ferritin concentration is genetically associated with increased concentrations of C-reactive protein (CRP) and complement component 3 (C3) 2.
• Serum ferritin is considered a marker of cellular damage and is associated with inflammation, as it arises from damaged cells and correlates with biomarkers of cell damage and oxidative stress 3.
• Ferritin has been linked to various inflammatory diseases, including COVID-19, and its high levels in patients with severe COVID-19 may indicate a pathogenetic role rather than just an acute response to inflammation 4.

Mechanisms of Ferritin and Inflammation

• Ferritin may play a role in the inflammatory process, as it is involved in the regulation of iron levels and iron-induced cellular damage 5.
• Inflammation can affect ferritin levels, and adjusting ferritin for inflammation is important for accurately assessing iron status, particularly in settings with high prevalence of inflammation 6.
• The relationship between ferritin and inflammation is complex, and further research is needed to understand the mechanisms underlying this association and the potential role of ferritin in inflammatory diseases 2, 3, 4, 5.

Clinical Implications

• Ferritin levels can be used as a biomarker for inflammatory diseases, and its measurement may be useful in monitoring disease activity and response to treatment 3, 4.
• Adjusting ferritin for inflammation is important for accurately assessing iron status and diagnosing iron deficiency or excess, particularly in populations with high prevalence of inflammation 6.
• Further research is needed to explore the potential of ferritin as a target for host-directed therapies in inflammatory diseases 5.