期刊
MOLECULAR MEDICINE
卷 20, 期 -, 页码 486-489出版社
FEINSTEIN INST MED RES
DOI: 10.2119/molmed.2014.00121
关键词
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资金
- American Heart Association Scientist Development Grant [10SDG 3030051]
- Presidential Research Incentive Program of the Virginia Commonwealth University
- VCU Pauley Heart Center
- Victoria Johnson Research Laboratories
- Institutional National Institutes of Health K12 award [KL2RR031989]
- National Institutes of Health [AI-15614]
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 degrees 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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