PI3K and p38 MAPK are involved in simvastatin-enhanced IL-1β secretion. THP-1 cells were cultured for 24 hours in the presence or absence of simvastatin (10 μM) and stimulated for an additional 4 hours with 200 ng/mL LPS. When inhibitors were used, they were added either 1 hour before simvastatin or 1 hour before LPS treatment. Release of IL-1β was determined by ELISA; data are mean plus or minus SEM. (A) Absolute levels of IL-1β secretion (n = 8). (B) Relative inhibition of IL-1β secretion by PI3-kinase, p38 MAPK, and MEK1/2 inhibitors (n = 4, n = 4, and n = 3, respectively). (C) Relative inhibition of IL-1β secretion by PKC_ζ and mTOR inhibitors (n = 3 and n = 4, respectively). (D) Induction of LPS-induced IL-1β secretion by a GSK-3 inhibitor (n = 2). *P < .01 compared with 100%. There was no significant effect of the solvent DMSO, as demonstrated in Figure S2.