title: Drotrecogin alfa (activated) does not affect intracellular production of interleukin-6 and tumor necrosis factor-alpha in endotoxin-stimulated human monocytes.
abstract: In this ex vivo laboratory study, we investigated the effects of drotrecogin alfa (activated) (DA(a)), a recombinant form of human activated protein C, on the intracellular expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha on lipopolysaccharide (LPS)-stimulated human monocytes in a whole blood system. Whole blood samples from 10 healthy volunteers were stimulated with LPS (0.2 ng/mL) and incubated with 0.01, 0.1, 1, 10, and 100 nM of (final concentration) DA(a) for 3 h at 37 degrees C and 5% CO2. Intracellular expression of IL-6 and TNF-alpha was assessed by flow cytometry. Our investigation showed that DA(a), at any of the concentrations tested, did not affect intracellular IL-6 and TNF-alpha production in LPS-stimulated human monocytes after 3 h of incubation. The results of this investigation led us to conclude that any antiinflammatory activity of DA(a), if present, does not occur via detectible decreases in the production of proinflammatory cytokines IL-6 and TNF-alpha in human monocytes.
authors.affiliation: Departments of *Anesthesiology and Critical Care Medicine and †Cardiac and Thoracic Surgery, Martin Luther University Halle, Germany.
authors.forename: Elke G
authors.initials: EG
authors.lastname: Czeslick
authors.forename: Frank
authors.initials: F
authors.lastname: Nestler
authors.forename: Andreas
authors.initials: A
authors.lastname: Simm
authors.forename: Anja
authors.initials: A
authors.lastname: Struppert
authors.forename: Armin
authors.initials: A
authors.lastname: Sablotzki
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D011486:Protein C / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011486:Protein C; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; C421124:drotrecogin alfa activated