Lipopolysaccharide/endotoxin induces IL-18 via CD14 in human peripheral blood mononuclear cells in vitro

IL-18 shares activities with IL-12 in generating T-helper 1 cells and cytok ine response. It mediates LPS/endotoxin lethality by IL-12 independent inte rferon-gamma synthesis and it induces bacteria-related organ failure, As pe ripheral blood mononuclear cells (PBMC) are potent producers of IL-18, we s tudied the regulation of IL-18 upon exposure to LPS and Staphylococcus aure us (SAC) in vitro, Freshly isolated PBMC constitutively expressed IL-18 mRN A, After unstimulated preincubation for 48 h, however, IL-18 transcripts me re nearly not detectable by RT-PCR, but inducible by LPS or SAC (P<0.01). B oth LPS and SAC were potent stimuli of IL-18 protein secretion (P<0.01), LP S-mediated IL-18 gene expression and secretion was CD14-dependent and signi ficantly inhibited by co-incubation of PBMC with neutralizing CD14 antibody (P<0.01). We conclude that LPS-driven IL-18 is dependent on the expression of costimulatory factors and that IL-18 inhibition might attenuate IL-18-r elated toxic effects. (C) 2000 Academic Press.