Interleukin 2 (IL2) is the first effective immunotherapy approved to treat human cancers. But IL2 also disrupts the blood-brain barrier, causing brain edema due to vascular leak syndrome, which limits its use. How IL2 affects brain cells is not currently known.
Now, in a paper published in the Journal of Biological Chemistry, graduate student Lukasz Wylezinski and his mentor, Jacek Hawiger, M.D., Ph.D., show how IL2 alters the brain microcirculation.
They found that both human and mouse brain microvascular endothelial cells contain constituent proteins of the receptor that can bind and respond to IL2. Signaling through this IL2 receptor complex leads to activation of the pro-inflammatory protein nuclear factor kappa B, which turns on genes encoding mediators of inflammation.
Furthermore, IL2 disrupts the network of “floodgates,” adhesive proteins organized into adherens junctions that are critical in maintaining the blood-brain barrier. These findings may contribute to the development of new strategies to protect brain function while using IL2 to fight cancers.
The research was supported in part by National Institutes of Health grants CA068485, DK020593, DK058404, DK059637 and EY008126.
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