Effects of ethanol on monosodium urate crystal-induced inflammation

To investigate whether ethanol is able to decrease monosodium urate (MSU) crystal-induced inflammation, differentiated THP1 cells from a human monocyte cell line were cultured in the presence or absence of MSU crystals with and without ethanol. In an in vivo experiment, MSU crystals were administered into subcutaneous air pouches created in mice, following peritoneal injection of ethanol diluted with PBS. MSU crystals (0.75 mg/ml) stimulated the secretion of TNF-alpha, IL-8, and IL-1beta from THP1 cells, while ethanol at a concentration of 0.8% reduced those increases by 1.79-, 1.63-, and 1.75-fold, respectively. In vitro, MSU crystals (0.75 mg/ml) significantly increased the expression of phosphorylated JNK, ERK1/2, and p38 proteins in THP1 cells, while ethanol at a concentration of 0.8% reduced those increased expressions by 1.28-, 1.14-, and 1.68-fold, respectively. In addition, MSU crystals (0.75 mg/ml) significantly increased the expression of phosphorylated NF-kappaB protein in the nuclear and cytosolic fractions and decreased the expression of IkappaBalpha in the cytosolic fraction. Ethanol at a concentration of 0.8% reduced the MSU-increased expression of phosphorylated NF-kappaB in the nuclear and cytosolic fractions by 1.25- and 1.27-fold, respectively, while it also reduced the MSU-decreased expression of IkappaBalpha in the cytosolic fraction by 1.12-fold. In vivo, MSU crystals increased the number of leukocytes, as well as the concentrations of KC, MIP1alpha, and IL-6 in pouch fluids, while ethanol (5 g/kg body weight) considerably inhibited the MSU crystal-induced inflammation. These results strongly suggest that ethanol suppresses the secretion of inflammatory cytokines induced by MSU crystals via a pathway including MAPK (p38, JNK, and ERK1/2, especially p38) and NF-kappaB.