Letter Regarding Article by Franscini et al, “Gene Expression Profiling of Inflamed Human Endothelial Cells and Influence of Activated Protein C”

Abstract

To the Editor: We read with great interest the study by Franscini et al1 reporting novel antiinflammatory mechanisms of recombinant human-activated protein C (rhAPC)–dependent gene regulation in human endothelial cells. Some aspects of this work deserve further comment. The rhAPC preparation used by the authors is registered for use in patients (Xigris, Eli Lilly) and may contain traces of bovine thrombin resulting from the manufacturing process. The addition of the direct thrombin inhibitor hirudin would have excluded any residual thrombin activity in the rhAPC preparation in experiments by Franscini et al.1 Concentrations of rhAPC used by the authors were much higher (2.5 to 20 μg/mL) than median plasma levels (≈45 ng/mL) in patients. Laboratory data from the recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial demonstrated that a strong basis for systemic antiinflammatory effects for rhAPC is still missing.2 Thus, it …