Fluvastatin-mediated suppression of IgE-induced cytokine production can be enhanced by TGFβ1 (HYP3P.403)

Abstract Fluvastatin, an HMG-CoA reductase inhibitor known for its role in the treatment of hypercholesterolemia and cardiovascular disease, has recently been shown to play a role in the immune response. Given the critical role that mast cells play in allergy and inflammatory diseases such as asthma, we assessed the effect of Fluvastatin on mast cell function. We also examined the impact of TGFβ1, a cytokine we have previously shown capable of limiting mast cell function, in combination with Fluvastatin. We find that Fluvastatin suppresses IgE-mediated cytokine production in mouse mast cells. Prior exposure to TGFβ1 enhanced the effects of Fluvastatin, such that the IC50 for Fluvastatin-mediated suppression was 3-4-fold lower in the presence of TGFβ1 than in its absence. Interestingly, this effect was found for IgE-induced production of IL-6 and TNF, while TGFβ1 did not alter the suppressive effects of Fluvastatin on IL-13 or MCP-1. Current experiments seek to unravel the mechanism behind this selective effect of TGFβ1.