To the editor
The article by Miele et al.1 in the March 2001 issue of Nature Medicine proposed that erythroid differentiation-related factor (EDRF) is a molecular marker of transmissible spongiform encephalopathies (TSEs). They demonstrated a decrease in the expression of EDRF in scrapie-infected mice, and in sheep with scrapie and cattle with bovine spongiform encephalopathies as compared with healthy control animals. The down regulation of EDRF could be detected in blood samples from the infected animals and the authors suggest that EDRF might be useful in non-PrPSc–based preclinical diagnosis. However, the question of whether the finding is specific to prion-related diseases or related to a nonspecific inhibition of erythropiesis requires further studies, because no disease controls were included, such as animals with various infectious, inflammatory and malignant diseases. An explanation for the result might in fact be a nonspecific inhibition of erythropoiesis. We have demonstrated that interleukins 1-α and 1-β, in concentration ranges found in infectious and inflammatory states2,3,4,5, dose-dependently and selectively suppress the colony formation of the erythroid progenitor cells in bone marrow2. As the reduced EDRF levels in TSEs could, as also pointed out by Miele et al., represent a reduction in number of EDRF-expressing progenitors as well as a reduced EDRF expression, the finding might result from a non-specific cytokine-induced inhibition of marrow erythroid progenitors. In support of this view, Kim et al. recently reported an induction of mRNAs of proinflammatory cytokines, including interleukins 1-α and 1-β, in scrapie-infected mice6.
See Reply to “Is EDRF a specific marker for TSEs?” by G. Miele & M. Clinton
References
Miele, G., Manson, J.C. & Clinton, M. A novel erythroid-specific marker of transmissible spongiform encehalopathies. Nature Med. 7, 361–364 (2001).
Maury, C.P.J., Andersson, L.C., Teppo, A.M., Partanen, S. & Juvonen, E. Mechanism of anaemia in rheumatoid arthritis: demonstration of raised interleukin 1beta concentration in patients and of interleukin 1 mediated suppression of normal erythropoiesis and proliferation of human erythroleukaemia (HEL) cells in vitro. Ann. Rheum. Dis. 47, 972–978 (1988).
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Maury, C.P.J. & Lahdevirta, J. Correlation of serum cytokine levels with hematological abnormalities in human immunodeficiency virus infection. J. Int. Med. 227, 253–257 (1990).
Kim, J.L. et al. Expression of cytokine genes and increased nuclear factor-κB activity in the brains of scrapie-infected mice. Brain Res. Mol. Brain Res. 73, 17–27 (1999).
Williams, A., VanDam, A.M., Ritchie, D., Eikelenboom, P. & Fraser, H. Immunocytochemical appearance of cytokines, prostaglandin E-2 and lipocortin-1 in the CNS during the incubation period of murine scrapie correlates with progressive PrP accumulations. Brain Res. 754, 171–180 (1997).
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Maury, C. Is EDRF a specific marker for TSEs?. Nat Med 7, 641 (2001). https://doi.org/10.1038/88971
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DOI: https://doi.org/10.1038/88971
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