Objective To explore the underlying linking mechanism of serum tumor necrosis factor-alpha (TNF-α)/interleukin-6 (IL-6) with iron overload in patients with transfusion-dependent diseases.

Methods A total of 106 patients with transfusion dependency were enrolled as the study subjects, including 12 cases of thalassemia (thalassemia group), 49 cases of aplastic anemia (AA group), and 45 cases of myelodysplastic syndrome (MDS group). Liver magnetic resonance imaging T2-weighted (MRI T2) values were employed to assess iron overload in all patients, who were subsequently categorized into ironoverload and non-iron overload groups based on the assessment. Iron metabolism indicators serum ferritin (SF) and erythropoietin (EPO) and serum levels of TNF-α and IL-6 were compared among the groups. Pearson correlation analysis was used to examine the correlations of TNF-α and IL-6 with EPO, SF and liver iron concentration (LIC). Multivariate Logistic regression analysis was applied to identify the influencing factors of iron overload in patients. The predictive value of serum TNF-α and IL-6 for iron overload in patients with transfusion-dependent diseases was evaluated using receiver operating characteristic (ROC) curve analysis.

Results Among the 106 patients, 35 exhibited no iron overload, while 71 developed iron overload. Specifically, in the thalassemia group, there were 6 cases of mild iron overload, 2 cases of moderate iron overload, and 2 cases of severe iron overload. In the AA group, there were 13 cases of mild iron overload, 12 cases of moderate iron overload, 7 cases of severe iron overload, and 1 case of extremely severe iron overload. In the MDS group, there were 16 cases of mild iron overload, 9 cases of moderate iron overload, and 3 cases of severe iron overload. The iron intake in the iron overload group was higher than that in the non-iron overload group, with a statistically significant difference (P < 0.05). The levels of EPO, TNF-α, IL-6 and SF in the iron overload group were significantly higher than those in the non-iron overload group (P < 0.05). Pearson correlation analysis revealed positive correlations between serum TNF-α and IL-6 with EPO (r=0.611, 0.400), SF (r=0.572, 0.434) and LIC (r=0.550, 0.308) in patients with iron overload (P < 0.05). Logistic regression analysis indicated that high iron intake as well as elevated levels of EPO, TNF-α and IL-6 were risk factors for iron overload (P < 0.05). ROC curve analysis demonstrated that the areas under the curve (AUC) for serum TNF-α, IL-6 and their combined prediction of iron overload in patients with transfusion-dependent diseases were 0.707, 0.679 and 0.870, respectively. The combined predictive performance of these indicators was superior to that of individual tests (P < 0.05).

Conclusion Serum TNF-α and IL-6 are closely associated with abnormal iron metabolism. High iron intake, along with elevated levels of EPO, TNF-α and IL-6 are risk factors for iron overload in patients with transfusion-dependent diseases. The combined use of serum TNF-α and IL-6 exhibits favorable predictive efficacy for iron overload in these patients.