Modified phospholipids as anti-inflammatory compounds.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Feige
Erez
E
VBL Therapeutics, Or Yehuda, Israel.
Mendel
Itzhak
I
George
Jacob
J
Yacov
Niva
N
Harats
Dror
D
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000138:chemical synthesis; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000517:prevention & control; D050197:Atherosclerosis / Q000188:drug therapy / Q000517:prevention & control; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005997:Glycerylphosphorylcholine / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000517:prevention & control; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000008:administration & dosage / Q000138:chemical synthesis; D011565:Psoriasis / Q000188:drug therapy / Q000517:prevention & control; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology
D000893:Anti-Inflammatory Agents; D010743:Phospholipids; D051193:Toll-Like Receptors; D005997:Glycerylphosphorylcholine; C552500:1-palmityl-2-(4-carboxybutyl)-sn-glycero-3-phosphocholine