TNFα and hereditary hemocromatosis

Possible interactions

L. Valenti, A. L. Fracanzani, A. Scaccabarozzi, P. Dongiovanni, G. Santorelli, G. Fiorelli, S. Fargion

Research output: Contribution to journalArticle

Abstract

The pathogenesis of the defect of iron metabolism in monocyte macrophages of patients with hereditary hemochromatosis (HHC), demonstrated by their low iron content and IRPs upregulation, and by the higher release of ferritin after erythrophagocytosis, is far from clear. Tumor necrosis factor a (TNFa) is involved in the regulation of iron metabolism of monocyte macrophages: it is able to modulate the synthesis of ferritin, transferrin and their receptors, the expression of HFE and to inhibit the release of iron from peritoneal macrophages. A possible defect of TNFa in HHC has been postulated on the basis of the lower TNFa release from LPS stimulated monocytes of patients affected by HHC than of controls. Recently, two polymorphisms in the TNFa promoter (at position 308 and 238, associated with an increased expression of TNFα, have been described and found to influence the clinical history of liver diseases of different etiology. In the hypothesis that TNFa may play a role in HHC, we determined 1) TNFα release from 24 hours LPS (5ng/mL) stimulated monocytes of 31 patients with HHC (21 C282Y/ C282Y) and 13 controls 2) the prevalence of TNFa polymorphisms in 64 unrelated patients and 94 controls and 3) the relation between the presence of TNFα polymorphisms and the clinical expression of the disease. TNFa release in C282Y/C282Y patients was significantly lower than in controls (362±211 vs. 603±273 pg/mL, P2+53; P=0.007) and a lower, but not significant, prevalence of cirrhosis and severe iron overload (30% vs 50%). In conclusion, our results suggest that TNFα may play a role in HHC, possibly influencing iron accumulation and the clinical history of the disease.

Original languageEnglish
JournalBlood
Volume96
Issue number11 PART II
Publication statusPublished - 2000

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Hemochromatosis
Tumor Necrosis Factor-alpha
Iron
Macrophages
Monocytes
Polymorphism
Ferritins
Metabolism
History
Defects
Transferrin Receptors
Iron Overload
Peritoneal Macrophages
Liver
Liver Diseases
Fibrosis
Up-Regulation

ASJC Scopus subject areas

  • Hematology

Cite this

TNFα and hereditary hemocromatosis : Possible interactions. / Valenti, L.; Fracanzani, A. L.; Scaccabarozzi, A.; Dongiovanni, P.; Santorelli, G.; Fiorelli, G.; Fargion, S.

In: Blood, Vol. 96, No. 11 PART II, 2000.

Research output: Contribution to journalArticle

Valenti, L, Fracanzani, AL, Scaccabarozzi, A, Dongiovanni, P, Santorelli, G, Fiorelli, G & Fargion, S 2000, 'TNFα and hereditary hemocromatosis: Possible interactions', Blood, vol. 96, no. 11 PART II.
Valenti L, Fracanzani AL, Scaccabarozzi A, Dongiovanni P, Santorelli G, Fiorelli G et al. TNFα and hereditary hemocromatosis: Possible interactions. Blood. 2000;96(11 PART II).
Valenti, L. ; Fracanzani, A. L. ; Scaccabarozzi, A. ; Dongiovanni, P. ; Santorelli, G. ; Fiorelli, G. ; Fargion, S. / TNFα and hereditary hemocromatosis : Possible interactions. In: Blood. 2000 ; Vol. 96, No. 11 PART II.
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