Valproic acid attenuates the expression of pro-inflammatory cytokines lipopolysaccharide-treated canine peripheral blood mononuclear cells (in vitro) and in a canine endotoxemia model (in vivo).

摘要: Abstract Valproic acid (VPA), a known histone deacetylase inhibitor, has been used as an anticonvulsant in dogs. VPA also anti-inflammatory properties, but there are no reports on the immunomodulatory effects of canine endotoxemia. In present study, we demonstrate that use significantly reduces production early-phase pro-inflammatory cytokines (TNF-α, IL-6) caused by lipopolysaccharide (LPS) stimulation both vitro and vivo. For was evaluated for 24 h LPS (100 ng/ml)-treated peripheral blood mononuclear cells (PBMCs) which isolated from 5 healthy Beagle decreased mRNA expression TNF-α IL-6 dose-dependent manner (p  Fourteen adult Beagles were studied vivo study; nine dogs received low dose (10 μg/kg/h) via continuous IV infusion 12 h to induce endotoxemia whereas normal saline controls. Four out 9 endotoxemic administered (50 mg/kg, IV) at 1 h along with infusion. Three hours after first administration VPA, expressions PBMCs (p = 0.033 vs. group). circulating (p = 0.044 group 3 h) protein 3 h (p = 0.034 group) 6 h (p = 0.026 post-treatment. Our study suggests attenuates model We speculate valproic may be useful reducing inflammatory cytokine levels sepsis.