The complex role of inflammation in Multiple Sclerosis

This week, I had the review article regarding Multiple Sclerosis, which can be found at this link: http://www.mult-sclerosis.org/news/Nov2002/FullTextInflammationinMS.html. First, some background about the disease. Multiple Sclerosis is a chronic autoimmune disease that attacks myelin sheaths of axons in the central nervous system. Symptoms range from numbness, balance and coordination problems,  bladder dysfunction, bowel dysfunction, pain, sexual dysfunction, emotional changes, depression, paralysis and loss of vision. How this disease progresses, the severity, and the specific symptoms vary from person to person and are very unpredictable, making it difficult to study. The cause of MS is unknown, yet researchers think there might be some genetic factors. Some interesting theories that have been disproved are owning a dog, allergies, exposure to heavy metals, physical trauma, and aspartame. Although a viral cause is still being researched, there is no evidence yet that supports this.  MS is 2-3 times more likely in women than men, with most people diagnosed between ages 20-50. In all parts of the world, MS is more common further away from the equator, which has led to some research on a possible link between MS and vitamin D. MS is most common in Caucasians of northern European ancestry. Although there is no cure yet, treatment exists to manage symptoms and prevent flare-ups. Rehabilitation is also very important in managing this disease. A website that I found, located at http://www.nationalmssociety.org/index.aspx, was very helpful and informative about this disease.

The article looked at the role of inflammation in Multiple Sclerosis and argued that not all inflammatory processes involved are detrimental. The researchers begin the article with a more in depth look at the pathogenesis of MS. The demylinated areas of the CNS contains inflammatory filtrates with myelin specific T cells, B cells secreting anti-myelin antibodies, and many nonspecific mononuclear cells.  The chronic inflammation in MS is caused by proretention and prosurvival factors prevent the apoptosis or emigration of these inflammatory cells. MS can basically be thought of as an inflammatory process that does not resolve. Here's how it happens:  cerebral endothelial cells regulate traffic and play an important role in maintaining the integrity of the blood brain barrier. Patients with MS have abnormal endothelial tight junctions, increasing leakiness and permeability. The damaged BBB allows mononuclear cells to enter the brain, and the inability to clear them results in an aggregation of lymphocytes, activating local immune cells like microglia and astrocytes. This sets the stage for an immune reaction in the CNS. The activated microglia act as phagocytes and begin to demyelinate the axons. The accumulation of leukocytes ultimately ends up with tissue hyperplasia, demyelination, axonal loss and astrocytic scarring. In the final mechanisms of damage, macrophages phagocytize myelin, anti-myelin antibodies are secreted, and release of myelin toxic  cytokines as well as nitric oxide.

I found the title of this article to be very fitting, because inflammation in MS is both good, bad, and extremely complex. The immense complexities of the inflammatory processes involved in MS can explain why so many of the treatments described in this review were unsuccessful or even dangerous.  One of the major complexities that I see with MS is that to treat this disease, the Central Nervous System must be accessed through the blood-brain barrier. Introducing things into the BBB, even if they could help, can be very dangerous and can cause many different side effects. Because there are so many interactions between immune cells in this disease, any treatment is likely to affect many more processes than the one it is intended for. This makes research and treatment very complex indeed. To anyone wanting to do research in this field, your contributions are much needed and you are a brave soul!