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

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.