Literature DB >> 25121719

Leukocyte activity in patients with ST-segment elevation acute myocardial infarction treated with anakinra.

Chiara Sonnino1, Sanah Christopher1, Claudia Oddi1, Stefano Toldo1, Raquel Appa Falcao1, Ryan D Melchior1, George H Mueller1, Nayef A Abouzaki1, Amit Varma1, Michael L Gambill1, Benjamin W Van Tassell1, Charles A Dinarello2, Antonio Abbate1.   

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.

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Year:  2014        PMID: 25121719      PMCID: PMC4277550          DOI: 10.2119/molmed.2014.00121

Source DB:  PubMed          Journal:  Mol Med        ISSN: 1076-1551            Impact factor:   6.354


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