Multiple Sclerosis and Inflammation

Multiple Sclerosis (MS) is an inflammatory autoimmune disease of the myelinated sheaths of neurons of the brain and nervous system. Anti-inflammatory dietary and lifestyle changes have a significant impact on prevention and treatment of MS.

A common criticism of the biomedical literature is the focus on therapy and cure rather than cause and prevention. This is evident with multiple sclerosis. This disease is dominated by an immunological attack on the insulating myelin sheaths of the nervous system. The symptoms increase in waves of increasing severity over a number of years. MS patients produce antibodies against a myelin basic protein. Risk factors include smoking, prior infection with Epstein-Barr virus (mononucleosis) and low vitamin D/sun exposure. Treatment focuses on the neurological symptoms of the disease. My interest is what caused the disease and an exploration of whether the subsequent removal of the initiating events can provide more effective therapy. Here is what I think happens, based in part on observations from other inflammatory autoimmune diseases.

The early events in many inflammation-based diseases include a disruption of the expression of heparan sulfate proteoglycans (HSPGs). One HSPG is a component of the extracellular matrix of the cells that line blood vessels and provides a barrier to prohibit cells and proteins from leaking from the blood serum into the brain, i.e. the blood/brain barrier. Inflammation blocks normal heparin synthesis by blood vessels, attacks the BBB and facilitates the recruitment of white blood cells, lymphocytes that can mount an immune attack on the brain.

Since HSPGs interact intimately with most proteins on the surface of cells and these binding interactions are the basis for signaling and internalization, changes in the HSPGs can disrupt the maintenance of immunological tolerance -- inflammation also leads to inappropriate immunological recognition, particularly of proteins with triplets of basic amino acids (strong heparin-binding domains common on nuclear proteins.) This is evident in diabetes, lupus and inflammatory bowel diseases (and also dozens of allergens.) In the case of MS the self-antigen is the myelin basic protein. The antibody binding portions of the myelin basic protein are similar to many nuclear proteins that would be expected by comparison to other autoimmune diseases and allergies to stimulate antibody production if exposed to the immune system during inflammation. Thus an immune attack on myelin in MS could be caused by trauma or viral infections in the brain that release cellular debris and cause inflammation. Subsequent flareups could be initiated by systemic inflammation that attacks the BBB and permits lymphocytes to leave the blood stream and attack the myelin.

The MS risk with smoking may be the unusual combination of potent carcinogens and inflammatory compounds with nicotine. These may have had an impact on the integrity of the BBB via chronic inflammation. Epstein-Barr virus exposure may also have affected the BBB and contributed to chronic inflammation. Vitamin D acts similarly to the steroid hormones in many ways and may have some powerful effects as an anti-inflammatory. It may act similarly to estrogen, which is a potent inhibitor of brain inflammation in response to trauma.

Omega-3 fatty acids of fish oil are now being tested as a treatment for MS. An anti-inflammatory diet and lifestyle may be a powerful deterrent to MS and may also be effective in reducing or reversing the progression of the disease.