LETTER TO THE EDITOR
Reply
Guenter Weiss, MD and
Hannes Gaenzer, MD
Department of Internal Medicine, University Hospital, Anichstrasse 35, A-6020 Innsbruck, Austria
guenter.weiss{at}uibk.ac.at
We agree with Dr. Auer and colleagues that ferritin levels in our study (1) may be both a reflection of increased iron stores linked to primary iron overload and an indication of a chronic inflammation, as ferritin expression is also regulated by inflammatory cytokines (2,3).
To rule out the possibility that increased ferritin levels in hemochromatotic patients are a reflection of an ongoing inflammatory response we performed conventional serum tests for C-reactive protein (CRP), which were all normal in the hemochromatotic subjects included in our study. However, we cannot rule out that by using a high-sensitive CRP assay we could have found low-grade inflammation not detected by the conventional test (4), which would have been of interest because, at least in diabetics, elevated levels of CRP have been associated with early structural changes of arteries (5) and because iron is known to increase formation of hydroxyl radicals during an inflammatory process (6), which will then exert harmful effects toward the endothelium.
However, in our study, changes in endothelial-dependent dilation (EDD) very well correlated with transferrin saturation in a way that higher transferin saturation (TfS) was associated with increased oxidative stress, increased intima-media thickness, and decreased EDD. This observation argues against an important role of inflammation in our setting. This notion is based on the fact that, during inflammation, drastic changes in iron homeostasis and distribution occur, which frequently lead to the development of anemia of chronic disease (7). This condition is characterized by high ferritin levels and low transferrin saturation, the later just being the opposite of what is observed in hemochromatotic patients, even in our study.
Finally, our data demonstrate a close relationship among iron overload, impaired EDD, and increased intima-media thickness, which may not be primarily referred to an underlying inflammatory condition. Nonetheless, determination of high-sensitive CRP will be attractive to see whether iron overload may induce low-grade inflammation in hemochromatotic patients.
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References
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1. Gaenzer H, Marschang P, Sturm W, et al. Association between increased iron stores and impaired endothelial function in patients with hereditary hemochromatosis. J Am Coll Cardiol. 2002;40:2189–2194[Abstract/Free Full Text]
2. Weiss G. Iron and immunity: a double-edged sword. Eur J Clin Invest. 2002;32(Suppl 1):70–78
3. Torti FM, Torit SV. Regulation of ferritin genes and protein. Blood. 2002;99:3505–3516[Free Full Text]
4. Berliner S, Zeltser D, Shapira I, et al. A simple biomarker to exclude the presence of low grade inflammation in apparently healthy individuals. J Cardiovasc Risk. 2002;9:281–286[Medline]
5. Hayaishi-Okano R, Yamasaki Y, Katakami N, et al. Elevated C-reactive protein associates with early-stage carotid atherosclerosis in young subjects with type 1 diabetes. Diabetes Care. 2002;25:1432–1438[Abstract/Free Full Text]
6. Eaton JW, Qian M. Molecular bases of cellular iron toxicity. Free Radic Biol Med. 2002;32:833–840[CrossRef][Medline]
7. Weiss G. Pathogenesis and treatment of anaemia of chronic disease. Blood Rev. 2002;16:87–96[CrossRef][Medline]
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