Statin treatment suppresses IgE-mediated mast cell activation in vitro and in vivo (HYP4P.316)

Abstract Statin drugs are HMG-CoA reductase inhibitors used in the treatment of hypercholesterolemia and cardiovascular disease. They have also been shown to suppress the immune response. Given the critical role that mast cells play in allergic and inflammatory diseases, we assessed the effect of statin drugs on mast cell function. We demonstrate that Fluvastatin suppresses IgE-mediated degranulation and production of pro-inflammatory cytokines and chemokines, without altering IL-10 secretion. These effects were reversed by the addition of mevalonic acid, and mimicked by geranyl geranyl tranferase blockade, suggesting that Fluvastatin inhibits lipid modifications to small G proteins downstream of HMG CoA reductase. In vivo studies further showed that Fluvastatin suppressed IgE-mediated anaphylaxis. Interestingly, Fluvastatin-mediated suppression was completely absent in 129/SvJ mast cells, which showed a 2-fold induction of HMG CoA reductase upon statin treatment. Human mast cells from eight donors showed a range of responses to Fluvastatin, indicating that genetic background may influence statin-mediated suppression. These data demonstrate the possible use of statins, a widely-prescribed group of drugs, as a possible therapy for mast cell-associated disorders.