INVESTIGATING THE ROLE OF IRON HOMEOSTASIS IN ANEMIA OF CHRONIC DISEASE: MECHANISMS AND THERAPEUTIC TARGETS

Abstract

The common inflammatory disease complication Anemia of Chronic Disease (ACD) results in iron sequestration and elevated hepcidin levels while causing impaired erythropoiesis despite adequate iron stores. The inflammatory cytokines including interleukin-6 (IL-6) primarily cause functional iron deficiency by disrupting systemic iron homeostasis. The research evaluated how iron biomarkers interact with inflammatory mediators and therapeutic results in patients who have ACD. Cross-sectional observational research analyzed 120 adult chronic illness participants who had both clinical evidence of anemia and diagnoses of chronic kidney disease, rheumatoid arthritis and inflammatory bowel disease. The laboratory analysis of blood samples included measurements of hemoglobin and serum ferritin together with transferrin saturation (TSAT) and hepcidin and IL-6 and TNF-α and reticulocyte count. The research divided patients into three treatment groups which included oral iron supplementation and intravenous (IV) iron therapy and intravenous (IV) iron therapy with IL-6 inhibition. The research showed that 78% of patients exhibited elevated hepcidin levels especially among those who did not receive anti-inflammatory therapy (p < 0.01).

The majority of patients (67%) presented with ferritin levels above 200 ng/mL yet 72% showed TSAT below 20% which reflects functional iron restriction. Patients who received IV iron treatment combined with IL-6 inhibition achieved the highest hematologic improvement as their mean hemoglobin levels increased by 1.8 g/dL. The strong relationship between IL-6 and hepcidin levels (r = 0.82) confirmed inflammation as the primary factor in iron regulation disturbances. The research data demonstrates that dual-targeted therapy which treats inflammation and iron deficiency shows promise for erythropoiesis recovery in patients with ACD.