Multiple Sclerosis Progression Linked to MIF

A study suggests that a substance made by immune cells plays a
key role in the progression of a disease in animals that closely
mimics multiple sclerosis.
The findings further suggest that blocking the molecule, known as
macrophage migration inhibitory factor ( MIF ) might prevent the
progression of the disease.

Researchers at The Ohio State University Medical Center conducted
the study using mice that develop a disease that mimics multiple
sclerosis. They compared these animals to similar mice that
lacked MIF, an immune-system signaling molecule.

The results show that the animals without MIF develop the
initial, acute phase of the disease, but then show no signs of
further progression.

" Our results suggest that MIF may be less important for
initiating multiple sclerosis, but that it may be necessary for
multiple sclerosis progression," says principal investigator
Caroline C. Whitacre.

" These findings indicate that in the future we can perhaps use
MIF levels to predict the onset of a relapse. But more
importantly, perhaps this study will lead to drugs that can halt
the course of multiple sclerosis by blocking the action of MIF."

In about 85 percent of cases, multiple sclerosis shows a pattern
of remission and relapse, with no warning as to when a relapse
will occur.

For this study, Whitacre and a group of colleagues used mice that
develop the multiple sclerosis-like condition known as
experimental autoimmune encephalomyelitis ( EAE ). The mice
develop the disease after being inoculated with a myelin protein.
The researchers compared these mice to mice that were identical
except that they lacked the gene for MIF.

After inoculation, the mice with the MIF gene showed progressive
EAE. In contrast, the mice lacking the MIF gene showed signs of
early disease, but after about 20 days, these mice recovered and
showed no further sign of progression.

The study also gave the investigators insights into the mechanism
by which MIF influences the course of disease. They found that
MIF blocked the steroid hormone, corticosterone ( known as
cortisol, in humans ). Animals missing MIF had high levels of the
steroid, while those with MIF showed very low levels.

The level of the steroid hormone, in turn, caused important
immune-system changes in the animals that are likely to affect
the disease.

For example, the mice with MIF ( and low levels of the steroid
hormone ) showed high levels of immune-system cytokines or
products that promote inflammation. Mice that lacked MIF ( and
had high levels of the steroid ), on the other hand, showed high
levels of immune-system cytokines or products that suppress

" Our evidence overall suggests that the inhibition of this
steroid hormone by MIF has an important influence on the immune
system and in determining whether the disease progresses or not,"
Whitacre says.

Source: Ohio State University, 2005


Submitted  10/29/2005 9:22:00 PM