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Modified phospholipids as anti-inflammatory compounds

Feige, Erez; Mendel, Itzhak; George, Jacob; Yacov, Niva; Harats, Dror

Current Opinion in Lipidology:
doi: 10.1097/MOL.0b013e32833f2fcb
Therapy and clinical trials: Edited by Anton F. Stalenhoef and John J.P. Kastelein
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.

Author Information

VBL Therapeutics, Or Yehuda, Israel

Correspondence to Dror Harats, VBL Therapeutics, 6 Jonathan Netanyahu St., Or Yehuda 60376, Israel Tel: +972 3 6346450; fax: +972 3 6346449; e-mail: dror@vblrx.com

© 2010 Lippincott Williams & Wilkins, Inc.