Interferon could be a key to preventing or treating multiple sclerosis

October 29, 2008

Multiple sclerosis (MS) results when the body's own defense system attacks nerve fibers in the brain and spinal cord. Now scientists led by John Russell, Ph.D., at Washington University School of Medicine in St. Louis have shown that interferon-gamma plays a deciding role in whether immune cells attack and injure the central nervous system (brain and spinal cord) in mice.

Interferon-gamma is an immune system protein that helps the body defend itself from invaders. In their latest research, which appeared in the October issue of the Journal of Experimental Medicine, the researchers show that interferon-gamma determined whether activated immune cells -- previously primed to go after nerve cells -- would actually cause nerve damage in experimental mice.

The researchers found that in the cerebellums and brainstems of the mice, interferon-gamma was protective. However, in the spinal cord, interferon-gamma had the opposite effect, permitting nerve cell damage.

"Some studies show that the most serious cases of MS in people occur when the immune system specifically targets the cerebellum, a part of the brain responsible for sensory perception, coordination and movement control," says Russell, professor of developmental biology. "Our study suggests that researchers need to look at the amount of interferon-gamma produced in the cerebellum and other brain regions in people with MS."

The researchers studied mice genetically engineered to be physiologically "blind" to interferon-gamma -- the mice had none of the usual receptors on their cells that recognize and respond to interferon-gamma. So in these mice it was as though interferon-gamma didn't exist.

In the interferon-insensitive mice, immune cells primed to attack nerves and then injected into the mice's veins were able to get into the cerebellum and brain stem and initiate nerve cell damage leading to MS-like disease.

In comparison, in mice with normal interferon-gamma recognition, immune cells were prevented from entering the brain and causing problems. The exact mechanism to account for this is still under study.

"Down the road, we would like to investigate whether we can prevent disease in the cerebellum in mice if we promote interferon production in that brain region," Russell says. "One way to do that would be to use gene therapy to insert a gene that would increase interferon in the mice's brains. Then we would test the mice to see if they gained protection against MS-like disease."

In contrast to its protective role in the brain, in the spinal cord interferon-gamma helped instigate nerve damage. In mice with intact interferon-gamma recognition, activated and injected immune cells were able to enter the spinal cord and cause injury. In mice without interferon recognition, the immune cells were unable to initiate spinal cord inflammation, and no damage occurred.

"Our research shows that certain characteristics inherent in different regions of the brain and spinal cord can provoke immune attacks on nerve cells," Russell says. "An understanding of the mechanisms involved in immune system invasion of the nervous system may allow development of better models for determining prognosis and treating many neurological diseases such as multiple sclerosis."

This latest research bolsters Russell's central hypothesis about MS and related disorders, which goes against some widely held assumptions. He holds that in physiological circumstances that ultimately lead to MS, the central nervous system itself allows or even aids immune system attacks.

"A scientifically popular view of how MS occurs is that the immune system somehow gets armed against normal brain antigens and attacks neurons," Russell says. "In that view, brain cells have a passive role. But in this and previous research, we've shown that there's a 'conversation' between the immune system and the central nervous system and that molecular signals passed between them are involved in the development of MS-like disease in mice."
-end-
Lees JR, Golumbek PT, Sim J, Dorsey D, Russell JH. Regional CNS responses to IFN-γ determine lesion localization patterns during EAE pathogenesis. Journal of Experimental Medicine. 2008 Oct 27;205(11):2633-2642.

Funding from the National Multiple Sclerosis Society and the National Institutes of Health supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Washington University School of Medicine

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.