A substance secreted by cells that make up the immune system may play an important role in the progression of multiple sclerosis (MS), according to research published this month.¹

The findings also suggest that blocking this substance, known as macrophage migration inhibitory factor, or MIF, might help prevent the advancement of MS.

"These findings indicate that in the future, we can perhaps use MIF levels to predict the onset of a relapse," explained the study's lead researcher, Caroline Whitacre, PhD, a professor of Molecular Virology, Immunology, and Medical Genetics at Ohio State University. "But more importantly, perhaps this study will lead to drugs that can halt the course of MS by blocking the action of MIF."

A Key Player?
Whitacre and her colleagues conducted their analysis of this immune system substance by using mice that can develop a disease similar in pathology to MS known as experimental autoimmune encephalomyelitis (en-sef-uh-loh-my-uh-LITE-iss) (EAE). The mice developed EAE after being inoculated with a myelin protein. The study then compared the course of the disease in mice with MIF compared to rodents that lacked this substance.

The results showed that the animals that lacked this compound developed the initial, acute phase of EAE, similar to what happens in MS, but they then showed no signs of further progression. By contrast, those with MIF in their bodies had progressive EAE, Whitacre and her colleagues reported.

The Influence of MIF
The study also gave the scientists some insight into the mechanisms behind how MIF influences the course of EAE. They learned that the substance blocks a steroid hormone called corticosterone (known as cortisol in people). Animals missing MIF had high levels of corticosterone, and vice-versa.

Depending on the level of the steroid hormone in these mice, it caused significant changes in the animals' immune systems that the investigators speculated had some influence on the course of EAE.

The Inflammatory Link
For example, mice with MIF (and very low levels of corticosterone) had high levels of pro-inflammatory cytokines, proteins made by certain immune system cells that promote inflammation. In contrast, rodents that lacked MIF (and had very high levels of corticosterone) had significantly high levels of anti-inflammatory cytokines, immune system proteins that suppress inflammation.

"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 explained.

Autoimmunity in MS
The origins of multiple sclerosis aren't exactly known, but immune system cells are a focus of scientific research on the disease because it's believed to be autoimmune in nature. Experts speculate that the immune system, for an unknown reason, goes awry, attacking tissue in the central nervous system, damaging or destroying it, rather than disease-causing organisms as it's supposed to.

Some of the targets in this part of the body by immune system cells include myelin, a fatty substance that surrounds and protects nerve fibers in the central nervous system and helps them communicate with one another, as well as oligodendrocytes, cells that manufacture myelin. When these parts of the central nervous system become damaged, it is manifested in the symptoms seen in multiple sclerosis.

The study was published as a Cutting Edge paper in the November 1 issue of the Journal of Immunology.

1. Powell ND, Papenfuss T, McClain MA et al. Cutting edge: macrophage migration inhibitory factor is necessary for progression of experimental autoimmune encephalomyelitis. J Immunol 2005 Nov 1;175(9):5611-4.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.