Elevated erythropoietin and cytokines levels are related to impaired reticulocyte maturation in thalassemic patients

Serum EPO concentration is related primarily to the rate of erythrocyte production and, under the stimulation of hypoxia, increases exponentially as hemoglobin (Hb) decreased. The level of EPO was determined in 141 subjects including 43 normal, 44 thalassemic patients and 54 thalassemic trait subjects. The EPO level was significantly higher in the thalassemic patients (54.8 mU/ml in HbH disease [α thal1/α thal2;], 78.1 mU/ml in HbH with Hb CS [α thal 1/CS]; 95.6 mU/ml in β-thal/HbE splenectomized [BE(S)]; and 114.8 mU/ml in β-thal/HbE non-splenectomized [BE(NS)]as compared with 12.0 mU/ml in normal subjects. No significant differences were detected in thalassemic trait subjects. In addition, the levels of EPO in thalassemic patients is correlated significantly with the number of reticulocytes and the reticulocyte fractions especially the fraction of immature reticulocytes. Interestingly, the highest level of EPO/% retic ratio as indicated for EPO non-responder was detected in BE(NS) patients. However, the impaired reticulocytes maturation was found to be related significantly with the levels of TNF-α,IFN-γ,IL-10, and VEGF. Since, TNF-α, IFN-γ, IL-10 and VEGF are reported as the cytokines with erythropoietic inhibitory mediators, the variation of these cytokines in thalassemic environments may be associated to the anemic crisis in these patients.