Antibody Blocking Inflammation5 months ago
Posted on Jun 15, 2018, 12 p.m.
It has been discovered by researchers from the University of California that inflammation can be blocked naturally within model mice using an antibody that binds oxidized phospholipid molecules on cell surfaces which are modified by inflammation, as published in Nature.
The E06 antibody was observed to protect the model animals from arterial plaque formation, hardening of arteries and liver disease, and prolonged their lives even when the model animals were fed high fat diets. Findings uncover a potential new therapeutic approach to prevent of reverse a variety of diseases which are linked to inflammation which includes aortic stenosis, hepatic steatosis, and atherosclerosis.
Inflammation and oxidized phospholipid molecules seem to go hand in hand, that does not mean that OxPL is the cause, but it definitely plays a key role. Some phospholipid molecules are susceptible to modification by reactive oxygen species forming oxidized phospholipid molecules, which is common in inflammatory conditions in which artery blocking plaques form. Previously it was not possible to control phospholipid oxidation in a way that makes it possible to study its role in inflammation and atherosclerosis.
Model mice were fed high fat diets once they were engineered to have two attributes: a gene mutation making them appropriate models for atherosclerosis; and they generate a piece of E06 antibody enough to bind to OxPL and prevent ability to cause inflammation in immune cells but not enough to cause inflammation on its own.
Model mice with E06 antibodies had 28-57% less atherosclerosis even after one year with high cholesterol levels. Antibody E06 decreased aortic valve calcification, hepatic steatosis, and liver inflammation. E06 mice had 32% less serum amyloid A, which is a marker for systemic inflammation. E06 prolonged the animals lives, as after 15 months they were all alive vs 54% of the control animals.
According to the researchers this is the first time that oxidized phospholipid molecules have been shown to be pro-inflammatory and pro-atherogenic, and can be counteracted by E06 antibodies. Findings suggest therapies that are targeted to inactivate OxPL can be beneficial for reducing inflammation in general, and especially in cases of disease such as hepatic steatosis, atherosclerosis, and aortic stenosis.
E06 antibodies are currently being tested in model animals of human disease which are linked to inflammation including nonalcoholic steatohepatitis and osteoporosis.
Materials provided by University of California - San Diego.
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Xuchu Que, Ming-Yow Hung, Calvin Yeang, Ayelet Gonen, Thomas A. Prohaska, Xiaoli Sun, Cody Diehl, Antti Määttä, Dalia E. Gaddis, Karen Bowden, Jennifer Pattison, Jeffrey G. MacDonald, Seppo Ylä-Herttuala, Pamela L. Mellon, Catherine C. Hedrick, Klaus Ley, Yury I. Miller, Christopher K. Glass, Kirk L. Peterson, Christoph J. Binder, Sotirios Tsimikas, Joseph L. Witztum. Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice. Nature, 2018; DOI: 10.1038/s41586-018-0198-8