ω-3 fatty acids suppress inflammatory cytokine production by macrophages and hepatocytes

Objective: Long-term total parenteral nutrition (TPN) in children is often complicated by parental nutrition-associated liver disease and may even lead to liver failure. Recently, the addition of omega-3 fatty acids to TPN has been shown to reduce the risk of parental nutrition-associated liver disease. The purpose of this study was to explore the anti-inflammatory effects of omega-3 fatty acids (eicosapentaenoic acid [EPA]) to demonstrate the protection of the liver against hepatic steatosis and damage. Materials and Methods: Lipopolysaccharide (LPS) and prostaglandin E-2 (PGE(2)) were used to stimulate human macrophages and hepatocytes (THLE-3) to induce in vitro inflammatory condition. The cells were then incubated with either omega-3 (EPA) or omega-6 (arachidonic acid) fatty acids. Supernatants were collected at different time points for the measurement of tumor necrosis factor a (TNF-alpha), interleukin 6 (IL-6), and interleukin 10 (IL-10) using enzyme-linked immunosorbent assay. Furthermore, pretreated macrophages by LPS stimulation and after incubation with EPA were added to prestimulated hepatocytes for the subsequent measurement of cytokine response. Results: Eicosapentaenoic acid effectively reduced LPS-induced or PGE(2)-induced TNF-alpha and IL-6 expression, and increased IL-10 expression significantly when compared with arachidonic acid. Furthermore, supernatant collected after co-culturing EPA with macrophages also suppressed the levels of TNF-alpha and IL-6 in hepatocytes. This would suggest that EPA not only had an anti-inflammatory effect on macrophages and hepatocytes directly, it could indirectly reduce hepatocyte inflammation through activated macrophages. Conclusions: The addition of omega-3 fatty acids in TPN suppresses the inflammatory response via direct and indirect routes. The findings may help explain the clinical benefits of EPA in pediatric patients receiving long-term TPN. (C) 2010 Elsevier Inc. All rights reserved.