Caspase-1 activation and IL-18 induction by VTX-2337 leads to NK cell activation.

(A-D) The effects of caspase-1 inhibition on IL-1β, IL-18, IFNγ, and TNFα production by PBMC. Duplicate PBMC cultures from four healthy donors (indicated as D1, D2, D3 and D4) were treated overnight with medium (Ø), VTX-2337 (1 μM), or VTX-2337 plus z-VAD-FMK (10 μg/ml). Levels of IL-1β, IL-18, IFNγ, and TNFα in culture supernatant were measured by ELISA. (E-F) The effects of IL-18 blockade on VTX-2337-induced IFNγ and CD107a expression in NK cells. Summary graphs show the percentage of IFNγ+ and CD107a+ NK cells from PBMC cultured with medium (Ø), VTX-2337 (0.5 μM), or VTX-2337 and anti-IL18 neutralizing antibody (20 μg/ml) for 9 donors where each symbol represents one individual donor. The horizontal bar represents group the mean for the treatment. Data shown are the summary of four independent experiments from the 9 donors, *, p<0.05 by Wilcoxon signed-rank test.