Effects of caspase-1 inhibition on hepatic inflammation. LDLR−/−.Leiden mice were fed a high-fat diet for 21 weeks (HFD; n=15) or HFD+caspase-1 inhibitor Ac-YVAD-cmk (40 mg kg−1 daily) starting treatment after 9 weeks of HFD (HFD+YVAD; n=15). Low-fat diet (LFD)-fed mice (n=15) were included as a reference. (a) HFD-induced plasma alanine aminotransferase (ALAT) was reduced in HFD+YVAD. (b) Lobular inflammation (number of inflammatory foci per x100 field) was induced by HFD, this induction was prevented by Ac-YVAD-cmk treatment. (c) F4/80 mRNA expression did not differ between groups. (d) Representative photomicrographs of immunohistochemical analysis of MPO-positive neutrophils. (e) Quantification of the number of MPO-positive inflammatory foci (per x100 field) revealed a clear induction in HFD, which was not apparent in YVAD. (f) Hepatic Tnf-α mRNA was reduced in HFD+YVAD. All data are from the t=21 weeks time point and are mean±s.e.m. *P<0.05, **P<0.01, ***P<0.001 compared with HFD.