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Blocking crucial molecule could help treat multiple sclerosis, Jefferson neuroscientists say
Date:4/24/2011

ars in an advance online publication of Nature Immunology on April 24.

These findings identify the interleukin-23 (IL-23)/ Th17/GM-CSF axis as the major pathway in pathogenesis of autoimmune central nervous system inflammation and likely other autoimmune diseases. IL-23, a known cytokine that causes autoimmune inflammation of the brain, induces production of more GM-CSF in Th17 cells, the researchers explain.

Dr. Rostami, who is also director of the Neuroimmunology Laboratory in the Department of Neurology at JMC, and his colleagues used an animal model of MS called experimental autoimmune encephalomyelitis (EAE) for the investigation, a common model used to study the pathogenesis of the disease. Mice whose Th17 cells cannot produce GM-CSF did not develop neuroinflammation, thus GM-CSF is responsible for disease manifestation in this experimental model. This scenario suggests feed-forward loop of IL-23 and GM-CSF driving the pathogenic encephalitogenic immune response in the brain and spinal cord.

Another recently published paper in Nature Immunology by Dr. Rostami and his team unraveled a mechanism that may help fight MS. The researchers found that a protein known as interkeukin-27 (IL-27) helped block, not induce, the onset of symptoms in animals with an MS-like disease. While increasing levels of GM-CSF may cause the disease, as shown in the current paper, increasing IL-27 concentrations may help quell an over-active immune system, the researchers reported.

"That was the first time that we had direct evidence that by actively giving IL-27 like a drug, we can suppress EAE in mice," Dr. Rostami said.

If similar findings from this current study of GM-CSF are found in human blood samples, this approach could eventually also be shown to be useful in the clinical setting, Dr. Rostami explains.

Whether GM-CSF drives neuroinflammation in MS remains unknown, but the current findings highlight the potential t
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Contact: Steve Graff
stephen.graff@jefferson.edu
215-955-5291
Thomas Jefferson University
Source:Eurekalert  

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