Journal Article

Leukocyte Activity in Patients with ST-Segment Elevation Acute Myocardial Infarction Treated with Anakinra

Van Tassell, Benjamin W., Toldo, Stefano, Mueller, George H., Dinarello, Charles A., Varma, Amit, Melchior, Ryan D., Gambill, Michael L., Sonnino, Chiara, Christopher, Sanah, Oddi, Claudia, Abouzaki, Nayef A., Abbate, Antonio, Falcao, Raquel Appa

2014

Overview

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.

• Publisher: BioMed Central,Springer Nature B.V
• Subject: Aged / Anti-Inflammatory Agents - pharmacology / Bacterial infections / Biomedical and Life Sciences / Biomedicine / Cells, Cultured / Cytokines / Diabetes / Disease / E coli / Female / Gene Expression Regulation - drug effects / Heart attacks / Heart failure / Humans / Infections / Interleukin 1 Receptor Antagonist Protein - pharmacology / Interleukin-6 - metabolism / Leukocytes - drug effects / Lipopolysaccharides - pharmacology / Male / Middle Aged / Molecular Medicine / Research Article / Staphylococcus epidermidis - immunology / Systemic Inflammatory Response Syndrome - blood / Systemic Inflammatory Response Syndrome - immunology / Tumor necrosis factor-TNF