Triglycerides (TG) are implicated in the development ofatherosclerosis through formation of foam cells and induction ofmacrophage cell death. In this study, we report that addition ofexogenous TG induced cell death in phorbol 12-myristate13-acetate-differentiated THP-1 human macrophages. TGtreatment induced a dramatic decrease in interleukin-1β (IL-1β)mRNA expression in a dose- and time-dependent manner. Theexpression of granulocyte macrophage colony-stimulating factorand platelet endothelial cell adhesion molecule remainedunchanged. To identify signaling pathways involved inTG-induced downregulation of IL-1β, we added p38 MAPK,protein kinase C (PKC) or c-Raf1 specific inhibitors. We foundthat inhibition of p38 MAPK alleviated the TG-induceddownregulation of IL-1β, whereas inhibition of PKC and c-Raf1had no effect. This is the first report showing decreased IL-1βexpression during TG-induced cell death in a human macrophageline. Our results suggest that downregulation of IL-1β expressionby TG-treated macrophages may play a role during atherogenesis.