Benoit Massonnet1,6,*, Sylvain Normand1,*, Reinhard Moschitz1, Adriana Delwail1, Laure Favot1, Martine Garcia1, Nicolas Bourmeyster2, Laurence Cuisset3, Gilles Grateau4, Franck Morel1, Christine Silvain1,5, Jean-Claude Lecron1,6
European Cytokine Network, Vol.20, No.3, pp. 112-120, 2009, DOI:10.1684/ecn.2009.0162
Abstract Objective. The effects of statins (3-hydroxy-3-methylglutaryl coenzyme A reductase-HMGR-inhibitors)
on the inflammatory response remain unclear. HMGR is implicated in the mevalonate path-way,
directly upstream of cholesterol biosynthesis. We studied the impairment by this pathway of cytokine pro-duction
by peripheral blood mononuclear cells (PBMCs) and THP-1 cells. The aim was to identify a specific
cytokine “signature” of cells under simvastatin treatment in order to link pharmacological inhibition of the
mevalonate pathway and inflammation. Methods. Normal human PBMCs and THP-1 cells were cultured with
inhibitors of HMGR (simvastatin), geranylgeranyltransferase (GGTI-298), farnesyltransferase (FTI-277), and/or
caspase-1 (Z-VAD(Ome)-FMK). Following culture,… More >