Insights on inflammation – an expert view

Photo of Dr. Amit Bar-Or

Our immune systems are designed to fight off disease, and one way they do this is through a complex, highly controlled process known as inflammation. We know that in MS, the immune system misbehaves, and inflammation occurs not only to ward off harmful agents, but also to inflict damage on nerve tissues which comprise the brain and spinal cord.

Researchers around the world are trying to determine how inflammation drives MS disease. I met with esteemed neuroimmunologist Dr. Amit Bar-Or, who shared some valuable insight on inflammation and MS. As I mentioned in my last post, Dr. Bar-Or is both a research scientist and neurologist, which allows him to combine both clinical and laboratory expertise when trying to investigate the full impact of inflammation in MS. I wanted to know how far we’ve come in the last decade in terms of our understanding of inflammation, and what the future holds for this promising avenue of MS research. This was his response.

We have come a long way in our understanding of inflammation in MS disease. We are not where we want to be yet, but there are several areas of inflammation research that have seen significant progress:

1. We used to think that only the T-cells of the immune system were involved in MS. We knew that there were bad guy T-cells and good guy T-cells, and we focused a lot of time and energy into research that would change the bad T-cells to good ones or preventing the bad ones from entering the central nervous system. This was the primary treatment approach. We have since learned that it is not just the T-cells that drive MS, but other cells are involved and they likely work in cooperation with one another. One good example is the B-cell, which is similar to the T-cell but has different responsibilities in inflammation. It is very clear now that if you remove just the B-cells from an MS patient, there is much less new disease activity. This does not mean that B-cells work alone in MS, but that B-cells work may be working in concert with T cells. It is likely that B-cells from people with MS have certain abnormalities that influence the harmful nature of T cells. So if we take away B-cells, we decrease the abnormal activity of T cells, which decreases new MS activity (new relapses). Now that we are aware that there are other important players contributing to MS disease, we try and target them therapeutically, which has been done successfully in the past. This work is still preliminary, however, and there is much more work to do.

2. We often associate inflammation with the relapsing-remitting form of MS, and view progressive MS as more of a degenerative process. In MS, Inflammation is traditionally viewed as a series of events that begins with the entry of reactive immune cells into the central nervous system (CNS), where they would cause tissue damage leading to relapses. New research shows that that there is inflammatory activity already occurring inside the CNS, which does not depend on entry of activated immune cells from the outside. Therefore there are now two types of inflammation associated with MS that must be considered:

a) Traditional view – outside activation of immune cells followed by trafficking into the nervous system
b) CNS compartmentalized view – inflammation that has set up shop inside the CNS and is unaffected by new waves of inflammation. Therefore if you stop new waves of inflammation to try and stop new relapses, inflammation in the brain will continue and this may explain progressive forms of MS

3. Scientists have recently discovered that the inflammation already occurring within the CNS involves a collection of immune cells that include T and B-cells. These cells are unaffected by current therapies because they target the immune cells that travel into the brain and spinal cord. There are new treatments in the pipeline which are known to get inside the CNS, which may be more effective in dampening the inflammatory activity happening within. Determining which cells are involved in the CNS-residing inflammation is absolutely critical in furthering the development of these new therapies.

4. We still do not know if breakdown of nerve tissue happens first (degeneration) or if inflammation. The genetic data has identified over 60 genes that are associated with risk for MS. From these studies we know that if you express many of these genes and not enough of the protective genes, you may be at risk for developing MS. Most of these genes are thought to be relevant to the immune system. This can argue that risk of developing MS is better linked with immune problems rather than degeneration problems. This is an area that needs to be explored further.

Categories Research

National vice-president, research, past MS researcher, and PhD in Cellular and Molecular Medicine from University of Ottawa. Leads the MS Society's research program to find the cure for MS and improve the quality of life for people affected by the disease.

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