Modified phospholipids as anti-inflammatory compounds

Curr Opin Lipidol. 2010 Dec;21(6):525-9. doi: 10.1097/MOL.0b013e32833f2fcb.

Abstract

Purpose of review: Oxidized phospholipids (OxPLs) are abundantly found at sites of inflammation and are considered to play an active role in the modulation of the immune response. Whereas most studies attributed a proinflammatory role to OxPLs, recent studies demonstrate that some products of phospholipid oxidation may in fact exhibit anti-inflammatory properties. This study summarizes the proinflammatory and anti-inflammatory properties of OxPLs and sheds light on the therapeutic potential of OxPL derivatives or analogs for treatment of chronic inflammatory disorders.

Recent findings: OxPLs may inhibit activation of several Toll-like receptors and can epigenetically reduce the capacity of dendritic cells to function as mature, fully functional immunostimulatory cells. These data demonstrate that OxPLs can induce anti-inflammatory effects. Moreover, VB-201, an orally available synthetic phospholipid analog of the Lecinoxoid family, was found to attenuate inflammation in various preclinical animal models and is currently employed in a phase II clinical trial in psoriasis.

Summary: Chemical or biological modifications of phospholipids yield various products, some of which may exhibit anti-inflammatory properties. Identification of such species and generation of more stable/potent anti-inflammatory OxPL variants may represent a novel approach for the treatment of immune-mediated diseases such as psoriasis, atherosclerosis, multiple sclerosis and rheumatoid arthritis.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents* / administration & dosage
  • Anti-Inflammatory Agents* / chemical synthesis
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / prevention & control
  • Atherosclerosis / drug therapy
  • Atherosclerosis / prevention & control
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Disease Models, Animal
  • Epigenesis, Genetic
  • Glycerylphosphorylcholine* / administration & dosage
  • Glycerylphosphorylcholine* / metabolism
  • Humans
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / metabolism
  • Mice
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / prevention & control
  • Oxidation-Reduction
  • Phospholipids* / administration & dosage
  • Phospholipids* / chemical synthesis
  • Psoriasis / drug therapy
  • Psoriasis / prevention & control
  • Rabbits
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Toll-Like Receptors / antagonists & inhibitors*
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology

Substances

  • Anti-Inflammatory Agents
  • Phospholipids
  • Toll-Like Receptors
  • VB-201
  • Glycerylphosphorylcholine