Topical atorvastatin ameliorates 12-O-tetradecanoylphorbol-13-acetate induced skin inflammation by reducing cutaneous cytokine levels and NF-κB activation

Atorvastatin is a 3-hydroxy-3-methylglutaryl coenzyme-A reductase inhibitor used in the treatment of atherosclerosis and dyslipidemia. Studies have evaluated the utility of statins in the treatment of skin inflammation but with varied results. In the present study, we investigated the effect of atorvastatin on TNF-alpha release and keratinocyte proliferation in vitro and in acute and chronic 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin inflammation in vivo. Atorvastatin significantly inhibited lipopolysacharide induced TNF-alpha release in THP-1 cells and keratinocyte proliferation in HaCaT cells. In an acute study, topical atorvastatin showed dose dependent reduction in TPA induced skin inflammation with highest efficacy observed at 500 A mu g/ear dose. In chronic study, topical atorvastatin significantly reduced TPA induced ear thickness, ear weight, cutaneous cytokines, MPO activity and improved histopathological features comparable to that of dexamethasone. Atorvastatin also inhibited TPA stimulated NF-kappa B activation in mouse ear. In conclusion, our results suggest that atorvastatin ameliorates TPA induced skin inflammation in mice at least in part, due to inhibition of cytokine release and NF-kappa B activation and may be beneficial for the treatment skin inflammation like psoriasis.