Simvastatin induces interleukin-18 production in human peripheral blood mononuclear cells.
The effects of statins on immune response depend on the inhibition of 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase and leukocyte function-associated antigen (LFA)-1, which is a ligand of intercellular adhesion molecule (ICAM)-1. Simvastatin, an HMG-CoA reductase inhibitor with mild inhibition of LFA-1, induced the production of interleukin (IL)-18, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma in human peripheral blood mononuclear cells (PBMC). The IL-18 production is located upstream of the cytokine cascade activated by simvastatin. Moreover, simvastatin concentration-dependently inhibited the expression of ICAM-1 and induced the expression of CD40 on monocytes. In the presence of IL-18, simvastatin suppressed the expression of ICAM-1 and CD40 as well as the production of IL-12, TNF-alpha and IFN-gamma in PBMC, contributing to the anti-inflammatory effect of simvastatin. The effects of simvastatin were abolished by the addition of the product of the HMG-CoA reductase, mevalonate, indicating the involvement of HMG-CoA reductase in the action of simvastatin.
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CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL GENE-Y GENE-Y GENE-Y GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL GENE-Y GENE-N GENE-Y GENE-Y GENE-Y GENE-Y CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL
simvastatin simvastatin simvastatin HMG-CoA Simvastatin HMG-CoA reductase leukocyte function-associated antigen (LFA)-1 intercellular adhesion molecule (ICAM)-1 HMG-CoA reductase LFA-1 mevalonate interleukin (IL)-18 tumor necrosis factor (TNF)-alpha interferon (IFN)-gamma IL-18 cytokine ICAM-1 CD40 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase IL-18 ICAM-1 HMG-CoA CD40 IL-12 TNF-alpha IFN-gamma HMG-CoA reductase interleukin-18 simvastatin HMG-CoA Simvastatin HMG-CoA simvastatin simvastatin 3-hydroxy-3-methylglutaryl coenzyme-A