Abstract

Thalassemia is an inherited blood disease characterized by low levels or absence of normal globin chains. Severe forms of thalassemia, thalassemia major (TM), require regular blood transfusions, the main cause of secondary hemosyderosis. However, iron overload is a potential complication, even in patients (pts) with thalassemia intermedia (TI), who do not require transfusions. Among them, iron overload is mainly the result of an excessive absorption of dietary iron, caused by a down-regulation of hepcidin, an hepatic hormone that acts as a major regulator of systemic iron homeostasis. Very low mRNA levels of hepcidin have been reported in urine as well as in liver biopsies from patients with TI. It has been also reported that, interleukin-1 alpha (IL-1α) stimulates hepcidin transcription, raising the question as to whether a down-regulation of this cytokine may be responsible, at least partially, for the excessive iron absorption occurring in patients with TI. Here, we assessed whether IL-1α was involved in hepcidin regulation in β-thalassemia. Peripheral blood mononuclear cells (PBMCs) were isolated from 6 TM pts, 8 TI pts and 6 controls. mRNA was obtained from PBMCs by RT-PCR. Hepcidin mRNA levels were reduced in both TM and TI pts when compared to the age matched normal controls. Neverthless, hepcidin mRNA levels were significantly lower in TI pts, as compared to TM pts receiving regular blood transfusions. Among TI pts lower hepcidin mRNA level was associated with lower level of IL-α. Tumor necrosis factor alpha (TNF-α) does not seem to be involved in the regulation of hepcidin transcription. Interestingly, the levels of mRNA expression of acyl-CoA-cholesterol acyltransferase (ACAT), the enzyme responsible for intracellular cholesterol ester accumulation, and thus, for atherosclerotic plaque formation were strongly induced in PBMCs in TI pts. These results suggest that PBMCs hepcidin and IL-1-α measurements could possibly be used in the future as simple, ease and sensible diagnostic tools for the detection of iron overload in patients with thalassemia. ACAT expression may even be used as therapeutic target in preventing atherosclerotic complications such as pulmonary thromboembolism, cerebral thrombosis, and leg ulcers. frequently occurring in such patients.

Disclosures: No relevant conflicts of interest to declare.

Author notes

Corresponding author