Selectively Blocking Inflammatory Signals May Protect Mice From MS

[Guest guest]

Posting this here since this list is about effect of

infection and inflammation so I think it is applicable.

http://www.medicalnewstoday.com/medicalnews.php?newsid=43159 & nfid=rssfeeds

<http://www.medicalnewstoday.com/medicalnews.php?newsid=43159 & nfid=rssfeeds>

Selectively Blocking Inflammatory Signals May Protect Mice

From MS

A new way to preserve the cells that surround and protect

nerves could

lead to new treatments for demyelinating diseases such a

multiple

sclerosis, a research team reports in the May 2006, issue of

the Journal

of Neuroscience.

The approach grew out of a novel explanation, quickly

gaining followers,

for the mechanism of nerve damage caused by multiple

sclerosis. Instead

of concentrating on the alterations that result in

autoimmune assaults

on the nervous system, researchers led by Popko of the

University

of Chicago

have focused on a set of factors that prevent recovery from

the inflammatory attacks.

A series of papers from Popko's lab has demonstrated that

interferon-gamma -- a chemical signal used to activate the

immune system

-- plays a critical role in damaging the cells that produce

myelin, the

protective coating that lines healthy nerves. Interferon not

only leaves

these cells, called oligodendrocytes, incapable of repairing

the damage

but can also kill them directly.

" Interferon-gamma is not normally found in the nervous

system, " said

Popko, the Jack Professor of Neurological Diseases at

the

University of Chicago, " but it can

gain entry after an inflammatory

flare-up. We previously showed how it harmed

oligodendrocytes. Here we

confirm its direct harmful effects on those cells and

demonstrate one

way of protecting them. "

The researchers produced a series of transgenic mice. In one

set they

introduced genes that produced interferon-gamma within the

central

nervous system. In another set they also introduced a gene

(known as

suppressor of cytokine signaling 1, or SOCS1) that blocked

the response

of myelin-producing cells to interferon-gamma.

Although transgenic mice with low levels of interferon-gamma

showed no

symptoms of nervous system damage, 18 out of 20 mice exposed

to higher

interferon levels developed difficulty walking, including

mild to

moderate tremors, within two weeks of birth. Only four out

of 20 mice

with both high interferon levels and the SOCS1 gene had

symptoms.

On autopsy, mice with high interferon levels in the nervous

system had

severe loss of oligodendrocytes, ranging from 20 to 40

percent. Those

with the protective SOCS1 gene lost only eight to 15

percent.

High interferon levels were also associated with loss of

myelin sheaths

around nerve connections and unprotected axons in the brain.

Again,

SOCS1 was able to reduce the damage.

" Together, " the researchers wrote, " these

data demonstrate that

oligodendroglial expression of SOCS1 protects mice from the

clinical and

morphological consequences of IFN-gamma expression in the

central

nervous system during development. "

" We found this tremendously encouraging, " said

Popko. " SOCS1 prevented

or reduced the harmful effects of interferon gamma on

myelin-producing

cells. This study solidifies our suspicions about

interferon's specific

role in demyelinating disease and suggests ways to block

it. "

Although there is currently no reliable way to deliver SOCS1

directly to

the nerves of a patient with multiple sclerosis, this

protective

approach could be combined with stem cell therapy to repair

nerve

damage. Several research groups are already studying the use

of stem

cells to repair damaged myelin sheaths, but in the long term

those stem

cells would be vulnerable to ongoing immune-mediated damage.

But if stem cells could be engineered to resist harmful

signals such as

interferon-gamma, they might be protected from the

" harsh environment "

present in immune mediated demyelinated lesions, said Popko.

###

The National Institutes of Health and the Myelin Repair

Foundation

supported the research. Additional authors include Roumen

Balabanov and

Ji Yeon Lee of the University of Chicago,

Krystal Strand of the

University of North Carolina, and April Kemper of Wake Forest

University.