Jan. 16, 2003 -- Starving saves mice from a kind of multiple sclerosis (MS), a new study shows. The finding adds convincing new evidence linking a fat-fighting hormone to MS and other autoimmune diseases.
In MS, the immune system attacks the body's own nerve linings. As in many other autoimmune diseases, it's one particular arm of the immune system that goes awry: the white blood cells called CD4+ T cells. These cells act as quarterbacks that choose targets and lead the attack. Researchers are trying to find out what sends these quarterbacks into action. The hope is that they can be pulled from the game before they do too much damage.
When the body has had enough food, it makes a hormone called leptin. Leptin abolishes appetite and makes the body lose weight. But those are far from its only effects. Leptin also kicks the immune system into high gear. Giuseppe Matarese, MD, and colleagues at Italy's National Research Council wondered whether this might be what puts the ball in play in MS. They looked at mice with experimental autoimmune encephalomyelitis (EAE) -- a viral disease that closely resembles MS.
"Before getting EAE symptoms, mice have a surge in leptin," Matarese tells WebMD. "There is increased leptin production in the brain. It is made there by [immune cells] that infiltrate the brain during disease."
Just as the body makes leptin when it's had enough food, it stops making leptin when it's starving. So if a leptin surge precedes MS-like disease, what would happen if the mice weren't eating? That's just what the Italian researchers did. They report their findings in the Jan. 15 issue of The Journal of Clinical Investigation.
"If you starve mice for 48 hours before inducing EAE, you can reduce the disease symptoms and reduce [immunity-caused] lesions in the brain," Matarese says.
It's a very important finding, says Stanford University's Lawrence Steinman, MD. Earlier this year, Steinman's lab reported that leptin genes become highly active in the brains of MS patients. This activity is found at the sites of active MS abnormalities.
In an editorial accompanying the Matarese team's study, Steinman and colleagues suggest that starving an autoimmune disease might protect against immune damage.
"I think that this is one of the remarkable ways our eating habits and metabolism tie into immunology," Steinman tells WebMD. "But these things are really complicated. Diet may be an important factor in MS, but in very different ways than people may expect. There is a tremendous amount to be learned. People with autoimmune diseases have to be cautious and shouldn't just start fasting until more is known."
One problem with fasting, Matarese says, is that mice had to lose a fifth of their body weight before they had significant disease protection. It takes only two days of fasting for a mouse to do this -- but for a human, that would mean two weeks of fasting.
The Italian researchers are looking for ways to block leptin's effects on the body. Steinman thinks a more natural approach -- dietary restriction -- would be safer and more natural. He's joined in that opinion by Harvard endocrinologist Jeffrey S. Flier, chief academic officer at Boston's Beth Israel Deaconess Medical Center. Like Steinman and Matarese, Flier is one of the first researchers to look at the link between leptin and immunity.
"A therapy aimed at blocking leptin would have many consequences other than improving autoimmunity -- it might make people obese," Flier tells WebMD. "Now, it could turn out that partial blocking wouldn't have too bad an effect on obesity, but would have a good effect on autoimmunity. But I wouldn't see it as a slam-dunk thing."
Meanwhile, Matarese is also looking at the other side of the coin. Leptin stimulation of immunity is bad for people with autoimmune diseases -- but it might be a good thing for people whose immune systems need a boost. His lab is now studying this possibility in animals.