Treatment with Oxidized Phospholipids Directly Inhibits Nonalcoholic Steatohepatitis and Liver Fibrosis Without Affecting Steatosis.

Background And Aims: Previous studies demonstrated that toll-like receptors 4 and 2 (TLR-4 and TLR-2), which are expressed on liver-resident Kupffer, hepatic stellate cells, and circulating monocytes, play a role in nonalcoholic fatty liver disease. Lecinoxoids are oxidized phospholipids that antagonize TLR-2- and TLR-4-mediated activation of innate immune cells and inhibit monocyte migration. In this study, we tested the effect of two functionally different lecinoxoids on the development of nonalcoholic steatohepatitis and liver fibrosis in a mouse model.

Inhibition of monocyte chemotaxis by VB-201, a small molecule lecinoxoid, hinders atherosclerosis development in ApoE⁻/⁻ mice.

Objective: Monocytes are motile cells which sense inflammatory stimuli and subsequently migrate to sites of inflammation. Key players in host defense, monocytes have nevertheless been implicated as requisite mediators of several chronic inflammatory diseases. Inhibition of monocyte chemotaxis is therefore an attractive anti-inflammatory strategy.