Drotrecogin alfa (activated) inhibits NF-kappa B activation and MIP-1-alpha release from isolated mononuclear cells of patients with severe sepsis

Objective and design: Non-anticoagulant biological activities, such as anti-inflammatory and anti-apoptotic mechanisms of action, have been suggested for recombinant human activated protein C (rhAPC; drotrecogin alfa (activated)). However, these mechanisms are much less characterized and understood than rhAPC’s anticoagulant activity. Aim of the study was to determine the effect of rhAPC on the activity of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB) in mononuclear cells isolated from septic patients and to characterize an effect downstream from NF-κB activation, such as the release of the NF-κB-controlled chemokine Macrophage Inflammatory Protein-1-alpha (MIP-1-α).