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(Circulation Research. 2005;97:e71.)
© 2005 American Heart Association, Inc.

Letters to the Editor

Letter to the Editor

In response to van den Berg et al:

Radjesh Bisoendial, John Kastelein, Erik Stroes

Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

An extract of the first 250 words of the full text is provided, because this article has no abstract.

We appreciate the interest of van den Berg and Taylor¹ in our article on the direct actions of CRP in humans.² In the context of numerous in vitro studies demonstrating that CRP elicits proatherogenic changes, our study was designed to examine the bioactivities of CRP in a human setting.

Van den Berg states that filtration methods are not very rigorous in removing endotoxin. However, the currently used purification process was successful in lowering the endotoxin burden by >97.5% within the recombinant human CRP (rhCRP) preparation to levels insufficient to cause any bioactivity in vivo, as demonstrated by standard methods. The final purified product was >97% pure by high-pressure size-exclusion chromatography (SEC-HPLC) and reverse-phase HPLC, whereas Time-of-Flight mass spectrometry provided supporting data for high purity, showing no other protein fractions besides the rhCRP.

Second, van den Berg poses that the kinetics of cytokine production observed on CRP-infusion fit the cytokine profile of endotoxin contamination. However, on comparison to endotoxin activities in humans, we show a clear disparity in cytokine profiles between that mediated by CRP and endotoxin.^2,3 Administration of endotoxin to animals as well as humans is invariably associated with rapid induction of TNF, a central and obligatory mediator that orchestrates a consistent sequence of events regarding cytokine production and coagulation activation.^3,4 Markedly, throughout all human CRP protocols, we were unable to detect any change in TNF expression, either at leukocyte mRNA levels or circulating plasma levels. Furthermore, heat-inactivation of the CRP preparation significantly diminished the capacity of CRP to . . . [Full Text of this Article]

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