Anemia of Inflammation – Causes, Symptoms & Treatment

What Is Anemia of Inflammation?

Anemia of inflammation – also referred to as anemia of chronic disease (ACD) – is a form of anemia that develops as a consequence of persistent inflammatory processes in the body. It is the second most common type of anemia worldwide, after iron-deficiency anemia. Unlike iron-deficiency anemia, anemia of inflammation is not primarily caused by a lack of iron, but rather by a disruption in iron utilization and a reduced production of red blood cells triggered by ongoing inflammation.

Causes

Anemia of inflammation typically occurs in the context of various chronic conditions. The most common underlying causes include:

• Chronic infectious diseases (e.g., tuberculosis, HIV, chronic hepatitis)
• Autoimmune disorders (e.g., rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease)
• Malignancies (cancers of various organs)
• Chronic kidney disease
• Heart failure

In these conditions, the body releases pro-inflammatory signaling molecules known as cytokines – including interleukin-6, interleukin-1, and tumor necrosis factor-alpha. These cytokines interfere with normal red blood cell production and promote the sequestration of iron within certain body cells, making it unavailable for the synthesis of hemoglobin.

Mechanism of Action

A key molecule in anemia of inflammation is the liver-derived hormone hepcidin. Inflammatory signals – particularly interleukin-6 – stimulate the liver to produce elevated levels of hepcidin. Hepcidin inhibits ferroportin, the protein responsible for transporting iron out of cells and into the bloodstream. As a result, iron becomes trapped inside macrophages and other cell types and is not available for red blood cell production, even when the body has sufficient iron stores overall.

In addition, inflammatory cytokines reduce the sensitivity of erythroid progenitor cells (red blood cell precursors) to erythropoietin (EPO), the primary growth hormone for red blood cells, and suppress its production by the kidneys.

Symptoms

The symptoms of anemia of inflammation are often nonspecific and may be attributed to the underlying condition. Common complaints include:

• Persistent fatigue and exhaustion
• Pallor of the skin and mucous membranes
• Shortness of breath and reduced physical capacity
• Dizziness and difficulty concentrating
• Headaches
• Increased heart rate (tachycardia)

Because the anemia is often mild to moderate in severity, symptoms may go unrecognized for extended periods of time.

Diagnosis

Diagnosis of anemia of inflammation is based on a combination of blood tests and clinical assessment of the underlying disease. Key diagnostic parameters include:

• Complete blood count (CBC): Reduced hemoglobin concentration and hematocrit. Red blood cells are typically normochromic (normal color) and normocytic (normal size), but may become hypochromic and microcytic in prolonged cases.
• Inflammatory markers: Elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)
• Iron studies: Low serum iron, elevated or normal ferritin (iron storage marker), low transferrin saturation, and low or normal transferrin – this pattern distinguishes ACD from pure iron-deficiency anemia
• Hepcidin levels: Often elevated (not routinely measured, but diagnostically helpful)
• Reticulocyte count: Low to normal, indicating impaired red blood cell production

Treatment

The most important therapeutic goal in anemia of inflammation is the treatment of the underlying condition. When the causative inflammatory disease is successfully managed, the anemia typically improves as well. Additional treatment options include:

Iron Supplementation

Iron supplementation is only appropriate when a true, laboratory-confirmed iron deficiency coexists with the inflammation-related anemia. Because oral iron is often poorly absorbed during active inflammation, intravenous iron administration may be preferred in such cases.

Erythropoiesis-Stimulating Agents

In certain patient populations – particularly those with chronic kidney disease or undergoing cancer treatment – erythropoiesis-stimulating agents (ESAs) such as epoetin alfa or darbepoetin alfa may be used to stimulate red blood cell production.

Blood Transfusions

In cases of severe, symptomatic anemia, a blood transfusion may be necessary to rapidly increase hemoglobin levels and ensure adequate oxygen delivery to the organs.

Emerging Therapies

Ongoing research is investigating the use of hepcidin antagonists and other targeted agents aimed at restoring normal iron metabolism in the context of chronic inflammation. However, most of these approaches are still in clinical development.

References

1. Weiss G, Goodnough LT. Anemia of Chronic Disease. New England Journal of Medicine. 2005;352(10):1011–1023.
2. Ganz T. Anemia of Inflammation. New England Journal of Medicine. 2019;381(12):1148–1157.
3. World Health Organization (WHO). Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Geneva: WHO Press; 2011.