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Topic Name: Jefferson researchers find anti-inflammation molecule helps fight MS-like disease

Category: Biomedical

Research persons: Abdolmohamad Rostami, M.D.,Ph.D.

Location: Jefferson Medical College, Thomas Jefferson University, United States

Details

An immune system messenger molecule that normally helps quiet inflammation could be an effective tool against multiple sclerosis (MS). Neurology researchers led by Abdolmohamad Rostami, M.D., Ph.D., professor and chair of the Department of Neurology at Jefferson Medical College of Thomas Jefferson University and the Jefferson Hospital for Neuroscience in Philadelphia, have found that the protein interkeukin-27 (IL-27) helped block the onset or reverse symptoms in animals with an MS-like disease.

The results suggest that IL-27 may someday be part of a therapy to temper over-active immune responses, which are thought to be at the heart of MS, an autoimmune disease (in which the body attacks its own tissue) affecting the central nervous system. The Jefferson neuroscientists report their findings November 11, 2007 in the journal Nature Immunology. The paper first appears in an advance online publication.

In MS, one of the most common neurological diseases affecting young adults, the myelin coating of nerve fibers becomes inflamed and scarred. As a result, “messages” cannot be sent through the nervous system. Dr. Rostami’s team was trying to understand the mechanisms of how immune responses damage the myelin sheath and axons in the brain.

They had previously observed that IL-27, a signaling molecule called a cytokine, could suppress IL-17, another cytokine, and inflammation. They also knew that in other MS models, mice that lacked receptors for IL-27 developed excessive inflammation.

Dr. Rostami, who is also director of the Neuroimmunology Laboratory in the Department of Neurology at Jefferson Medical College, Denise Fitzgerald, Ph.D., a postdoctoral research fellow in Dr. Rostami’s laboratory, and their colleagues used an animal model of MS called experimental autoimmune encephalomyelitis (EAE) for the investigation.

When the scientists gave IL-27 to the experimental mice, it significantly suppressed active disease. They saw similar effects from IL-27 in cultured cells that were transferred into “naïve” animals, which then produced significantly milder disease. At the same time, they also showed that IL-27 enhanced the production of IL-10, a crucial anti-inflammatory cytokine.

“We previously showed that IL-27 could suppress IL-17,” he notes. “Here we also show that IL-27 can enhance the production of IL-10. These may both be different and complementary mechanisms by which IL-27 can suppress EAE.”

The findings suggest that increasing IL-27 concentrations might raise IL-10 levels, and help quell an over-active immune response. “This is the first time that we have direct evidence that by actively giving IL-27 like a drug, we can suppress EAE in mice.”

Dr. Rostami explains that after an MS flare-up, patients recover from the disease, though the reasons are poorly understood. “We think that one of the ways that recovery from a disease flare-up occurs is that part of the immune system is shut off, suppressing the immune response in the brain. IL-27 appears to be crucial in this process,” he says.

The team would like to study MS patients’ blood samples to see if similar processes are at work, Dr. Rostami notes. “If we get similar findings in human disease, then perhaps IL-27 could be used therapeutically as a compound to suppress inflammation in the brains of MS patients.”

Note for Multiple sclerosis

Multiple sclerosis (abbreviated MS, also known as disseminated sclerosis or encephalomyelitis disseminata) is a chronic, inflammatory, demyelinating disease that affects the central nervous system (CNS). MS can cause a variety of symptoms, including changes in sensation, visual problems, muscle weakness, depression, difficulties with coordination and speech, severe fatigue, cognitive impairment, problems with balance, overheating, and pain. MS will cause impaired mobility and disability in more severe cases.

Multiple sclerosis affects neurons, the cells of the brain and spinal cord that carry information, create thought and perception, and allow the brain to control the body. Surrounding many of these neurons is a fatty layer known as the myelin sheath, which helps neurons carry electrical signals. MS causes gradual destruction of myelin (demyelination) and transection of neuron axons in patches throughout the brain and spinal cord. When the myelin is destroyed, the neurons can no longer effectively conduct their electrical signals. The name multiple sclerosis refers to the multiple scars (or scleroses) on the myelin sheaths. This scarring causes symptoms which vary widely depending upon which signals are interrupted.

Note for Interleukin-27

Interleukin-27 (IL-27) is a heterodimeric cytokine belonging to the IL-12 family that is composed of two subunits, Epstein-Barr virus (EBV)-induced gene 3 (EBI3) (also known as IL-27B) and IL27-p28 (also called IL-28). IL-27 plays an important function in regulating the activity of B and T lymphocytes. The effects of IL-27 are eliciting by its interaction with a specific cell surface receptor complex composed of two proteins known as IL-27R and gp130. The gene symbol IL27 refers to the IL-30 subunit of IL-27.

Note for Experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is an animal model of brain inflammation. It is an inflammatory demyelinating disease of the central nervous system (CNS). It is mostly used with rodents and is widely studied as an animal model of the human CNS demyelinating diseases, including the disease multiple sclerosis. EAE was motivated by observations during the convalescence from viral diseases by Thomas M. Rivers, D. H. Sprunt and G. P. Berry in 1933. Their findings upon a transfer of inflamed patient tissue to primates was published in the Journal of Experimental Medicine article (Vol. 58, No. 1, pp. 39-56). It was previously referred to as Experimental allergic encephalomyelitis. EAE can be induced by inoculation with whole CNS tissue, purified myelin basic protein (MBP) or myelin proteolipid protein (PLP), together with adjuvants. It may also be induced by the passive transfer of T cells specifically reactive to these myelin antigens. EAE may have either an acute or a chronic relapsing course. Acute EAE closely resembles the human disease acute disseminated encephalomyelitis, while chronic relapsing EAE resembles multiple sclerosis. EAE is also the prototype for T-cell-mediated autoimmune disease in general.

About Researcher:

Abdolmohamad Rostami

Professor and chair of the Department of Neurology, Jefferson Medical College
Thomas Jefferson University
Phone: 215-955-1234