G-2581

The Pivotal Role of IL-6 in Driving Anemia of Chronic Disease in Rheumatoid Arthritis: A First Report on Prevalence and Pathogenesis from Iran

 Narges Basirian ¹ ℗, Mohammad Javad Mousavi ² ©   

 
Abstract

3. Introduction: Anemia of chronic disease (ACD) is a debilitating comorbidity in rheumatoid arthritis (RA), potentially driven by proinflammatory cytokines, notably interleukin-6 (IL-6). IL-6 dysregulates iron homeostasis by inducing hepatic hepcidin, which restricts iron availability for erythropoiesis. Despite its global clinical significance, the prevalence and pathogenesis of ACD in RA patients have remain underexplored in Iran. This study addresses this critical knowledge gap, presenting the first report to investigate the prevalence of ACD and its association with IL-6 gene expression and serum levels, and disease severity in a cohort of Iranian RA patients. 4. Methods and Materials: In this pioneering cross-sectional study, a cohort of 100 RA patients was recruited. Based on key hematological and serological parameters, in particular hemoglobin (HGB), ferritin, and transferrin saturation (TSAT), patients were stratified into non-anemic, iron deficiency anemia (IDA), ACD, combined ACD/IDA, and other group. Disease activity was rigorously classified using the Disease Activity Score 28 (DAS28)-ESR into remission, low, moderate, and severe categories. IL-6 gene expression in peripheral blood mononuclear cells was quantified via real-time PCR, and serum IL-6 levels were assessed using a sandwich-type electrochemiluminescent (ECL). 5. Results: Our investigation revealed a significant burden of anemia, affecting 33% of patients. Notably, ACD was the most frequent subtype at 11%, followed by IDA at 9%, ACD/IDA at 6%, and other groups at 7%. A core finding was the significantly elevated IL-6 gene expression in anemic patients, especially the ACD group, compared to non-anemic controls (p = 0.0001 and p = 0.009, respectively). Both elevated IL-6 gene expression and serum levels were strongly associated with an increased risk of anemia and greater RA severity (p 0.05). Demonstrating a direct link to disease activity, IL-6 gene expression demonstrated a robust positive correlation with serum IL-6, swollen/tender joint counts, and the DAS28 score. Furthermore, elevated gene expression and serum levels of IL-6, ESR, and CRP, was significantly associated with both greater RA severity and an increased risk of anemia (p 0.05). Complementing these findings, the DAS28 score itself exhibited a strong negative correlation with a panel of anemia-related parameters, including HGB, hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), serum iron, and TSAT, confirming that higher disease activity is directly linked to a worsened hematological state. 6. Conclusion and Discussion: This first-of-its-kind study in Iran provides definitive evidence that elevated IL-6 is a central driver in the pathogenesis of ACD in RA patients. Our findings highlight the dual function of IL-6 in promoting both systemic inflammation and hepcidin-mediated iron blockade. These results not only establish the prevalence of ACD in RA patients but also underscore that targeting the IL-6 pathway is a crucial therapeutic strategy for managing both the articular and hematological manifestations of RA.

Keywords: Rheumatoid Arthritis, Anemia of Chronic Disease, Interleukin-6, Inflammation, First Report,