A unique chemical in the body may be the secret revealed in a new study¹ about why the immune system runs amok when multiple sclerosis strikes in the body. This chemical messenger frees some white blood cells from the body's normal restraints, allowing the immune cells to roam freely into the central nervous system, and then inflicting the damage seen in multiple sclerosis.

Aberrant Immunity
Experts speculate that MS is an autoimmune disease; certain cells of the immune system, normally designed to search out and attack disease-causing invaders like viruses and bacteria, instead attack healthy tissue in the body. The targeted tissue in the case of MS is a fatty substance known as myelin, which serves as a protective coating surrounding nerve fibers in the central nervous system (CNS). Myelin is not just a protectant, but also helps nerve fibers communicate with each other.² When myelin and the nerve fibers are damaged or destroyed, people with MS experience the symptoms of the disease:

• Bladder and bowel dysfunction
• Changes in cognitive function
• Dizziness and Vertigo
• Emotional problems
• Fatigue
• Difficulty walking
• Numbness
• Pain
• Sexual dysfunction
• Spasticity
• Vision problems2

Circumventing Normal Controls
In MS, the cells that bypass the body's normal constraints are known as T-effector cells. Scientists believe that when the disease strikes, T-effector cells damage myelin. Another group of white blood cells known as T-regulatory cells are supposed to hold T-effector cells back. But a chemical messenger known as interleukin-12 (IL-12) allows T-effector cells to roam freely into the CNS, circumventing T-regulatory cells.

"Normally, effector T-cells are under strict control as they circulate through the bloodstream in order to prevent unnecessary inflammation that could be harmful to otherwise healthy tissues," explained Benjamin Segal, MD, a neurologist at the University of Rochester who headed the study. "However, occasionally, they escape the body's suppression system. We're learning how they do that."

Segal was one of the first scientists to demonstrate that IL-12 played an important role in autoimmune diseases like MS.^3,4 He showed that this protein directed certain T-cells into the CNS, where they don’t belong, and attack myelin. He also demonstrated that animals without interleukin-12 are completely protected against a disease similar to MS. In contrast, exposing normally harmless T-effector cells to IL-12 appears to empower them to induce MS-like disease in mice.

A Drug That May Help?
In their latest study, Segal and neuroscience graduate student Irah King showed that IL-12's effects are more far-reaching in the body than first thought and affect some of the immune system's most powerful cells. The two researchers found that IL-12 gives T-effector cells the ability to avoid normal suppression by T-regulatory cells, whose job it is to keep the body from attacking itself.

IL-12 may also explain why patients who contract an infection may experience an MS relapse. When the infection occurs, IL-12 levels rise to help the body fend off the infection.

Segal and King are testing a drug in a group of patients that's designed to suppress IL-12. Doing so could restore the function of T-regulatory cells, allowing them to be more effective at keeping rogue T-effector cells in check. The scientists contend that such a medication may also be useful in other autoimmune diseases like Crohn's disease, psoriasis, and arthritis. IL-12, they speculate, may also play a role in these illnesses.

"There is a variety of treatments for MS, but most are only modestly effective," said Segal, an associate professor of Neurology and director of Neuroimmunology Research at the university. "We are always looking for better treatments that are more convenient for our patients, with fewer side effects. Inhibiting IL-12 offers one potential option."

One of the challenges in suppressing IL-12, though, is the fact that it would be compromising a person's immune system. In addition to its apparent destructive abilities in autoimmune disease, IL-12 is also instrumental at helping direct immune cells when an infection is present. As a result, there a treatment strategy is being devised with the aim of fighting off autoimmune disease while avoiding the need to weaken immunity, Segal explained. "We hope we will come closer to this goal by developing reagents that target specific molecules that appear to be critical for sustaining autoimmune inflammation (such as IL-12), as opposed to using global immunosuppressant agents (such as chemotherapies that have a broad effect on all bone marrow-derived cells)," he said.

"The hope is that by lowering IL-12 levels to a certain extent, central nervous system autoimmune inflammation will be curbed, but the immune system will retain sufficient reserves to fight off infections," Segal said.

1. King IA, Segal BM. Cutting edge: IL-12 induces CD4+CD25- T-cell activation in the presence of T-regulatory cells. J Immunol 2005 Jul 15;175(2):641-5.
2. National Multiple Sclerosis Society. What is Multiple Sclerosis? Available at: http://www.nationalmssociety.org/What%20is%20MS.asp. Accessed July 15, 2005.
3. Segal BM, Shevach EM. IL-12 unmasks latent autoimmune disease in resistant mice. J Exp Med 1996 Aug 1;184(2):771-5.
4. Segal BM, Dwyer BK, Shevach EM. An interleukin (IL)-10/IL-12 immunoregulatory circuit controls susceptibility to autoimmune disease. J Exp Med 1998 Feb 16;187(4):537-46.

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.