title: Leukocyte activity in patients with ST-segment elevation acute myocardial infarction treated with anakinra.
abstract: Anakinra, the recombinant form of the human interleukin (IL)-1 receptor antagonist, blunts the acute systemic inflammatory response in patients with ST-segment elevation myocardial infarction (STEMI), by determining a fall in peripheral blood leukocyte and plasma C-reactive protein levels. The aim of the present study was to determine the effects of anakinra on the activity of leukocytes measured ex vivo. Blood was collected 72 h after admission in 17 patients enrolled in the Virginia Commonwealth University-Anakirna Remodeling Trial (2) (VCU-ART2) and randomly treated with anakinra (N=7) or placebo (N=10). Whole blood was cultured at 37°C for 24 h to measure spontaneous production of IL-6 or stimulated with Escherichia coli lipopolysaccharide (LPS) for toll-like receptor (TLR)-4 or heat-killed Staphylococcus epidermidis (SE) for TLR-2 activation. The cultures of anakinra-treated patients produced significantly less IL-6 spontaneously (71 pg/mL [27-114]) compared with placebo-treated patients (290 pg/mL [211-617], p=0.005). LPS- or SE-induced IL-6 production, on the other hand, was not statistically different between anakinra-versus placebo-treated patients (344 pg/mL [94-560] versus 370 pg/mL [306-991], p=0.32 for LPS, and 484 pg/mL [77-612] versus 615 pg/mL [413-871], p=0.31 for SE, respectively). IL-1 blockade with anakinra in STEMI patients results in reduced spontaneous leukocyte activity ex vivo without impairing the responsiveness to bacterial stimuli.
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, Virginia, United States of America.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sonnino
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, Virginia, United States of America.
authors.forename: Sanah
authors.initials: S
authors.lastname: Christopher
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, Virginia, United States of America.
authors.forename: Claudia
authors.initials: C
authors.lastname: Oddi
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, Virginia, United States of America.
authors.forename: Stefano
authors.initials: S
authors.lastname: Toldo
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, Virginia, United States of America.
authors.forename: Raquel Appa
authors.initials: RA
authors.lastname: Falcao
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, Virginia, United States of America.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Melchior
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, Virginia, United States of America.
authors.forename: George H
authors.initials: GH
authors.lastname: Mueller
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, Virginia, United States of America.
authors.forename: Nayef A
authors.initials: NA
authors.lastname: Abouzaki
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, Virginia, United States of America.
authors.forename: Amit
authors.initials: A
authors.lastname: Varma
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, Virginia, United States of America.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Gambill
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, Virginia, United States of America.
authors.forename: Benjamin W
authors.initials: BW
authors.lastname: Van Tassell
authors.affiliation: Department of Medicine, University of Colorado, Aurora, Colorado, United States of America.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Virginia Commonwealth University, VCU Pauley Heart Center and Victoria Johnson Research Laboratories, Richmond, Virginia, United States of America.
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
mesh_terms: D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D013212:Staphylococcus epidermidis / Q000276:immunology*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides