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(Circulation Research. 2005;97:e115.)
© 2005 American Heart Association, Inc.

Letter to the Editor

Radjesh Bisoendial, Rakesh Birjmohun, Tymen Keller, Sander van Leuven, Han Levels, Marcel Levi, 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.

To the Editor:

We have diligently read the research commentary by Pepys et al,¹ which among others addresses the in vivo effects of C-reactive protein (CRP)- infusion into humans, as recently reported by us in a previous issue of this journal.² We would like to clarify some misconceptions surrounding our study, as generated in their report. Pepys et al observed, using recombinant human (rh)CRP that still contained large quantities of endotoxin, that this rhCRP solution induced an inflammatory reaction both in vitro as well as in mice, whereas CRP from human resources had no such effect. Pepys et al then extrapolate these findings to our study in humans and conclude that the in vivo effects of rhCRP we observed must have been caused by contaminants rather than rhCRP itself. In fact, these authors arrive at the wrong conclusion, and they fail to acknowledge several shortcomings in their own experiments.

First, their dialysed commercial rhCRP displayed residual endotoxin activity of 46·6 endotoxin units (EU) per mg of rhCRP and would for that sake never have been allowed for human use. In comparison, endotoxin activity of our rhCRP was 30x lower (<1·5 EU/mL), which resulted in less than 1·6 EU per mg of rhCRP (at a CRP concentration of 0·91 mg/mL). Interestingly, the trace amounts in our rhCRP are very similar to those reported by Pepys et al in their natural human (nh)CRP solution, ie, 0·9 EU/mg of nhCRP. Needless to state that extrapolation of their findings, using highly contaminated rhCRP, . . . [Full Text of this Article]

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