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Modified phospholipids as anti-inflammatory compounds

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

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

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.

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.