Figure 10.

Antagonism of agonist-stimulated IL-1β release from human whole blood, human diluted blood and THP-1 cells. Human whole blood or human blood diluted 10-fold with phosphate-buffered saline was stimulated with LPS (1 µg·mL⁻¹) for 80 min and then pre-incubated for 40 min with antagonist before measuring ATP-induced IL-1β release over a 30 min period. THP-1 cells were stimulated overnight with LPS (1 µg·mL⁻¹), harvested, pre-incubated for 40 min with antagonist before measuring BzATP-induced IL-1β release over a 30 min period. The pIC₅₀ of the antagonists was calculated at each concentration of agonist and is shown as a function of the agonist concentration. Agonist concentration is expressed relative to agonist EC₅₀ at each receptor such that log (Fold EC₅₀) represents logarithm (agonist concentration/agonist EC₅₀). (A) The effect of GSK314181. (B) The effect of GSK361390. The data are the mean ± SEM of 4–6 separate experiments. BzATP, 2′- & 3′-O-(4benzoylbenzoyl) ATP; GSK314181, 5-{[(3R)-3-amino-1-pyrrolidinyl]methyl}-2-chloro-N-(tricyclo[3.3.1.1^3,7]dec-1-ylmethyl)benzamide; GSK361390, N-adamantan-1-ylmethyl-2-chloro-5-(3,5-dioxo-4,5-dihydro-3H-[1,2,4]triazin-2-yl)-benzamide; IL-1β, interleukin-1β; LPS, lipopolysaccharide.