Inflammation

What is the Role of Inflammation in ALS?

Heidi Cartwright, Prince of Wales Medical Research Institute, Sydney Australia

Inflammation is part of the immune system's protective reaction to tissue damage or invasion by microbes. It is a process that should help heal. But sometimes the inflammation that accompanies illness or injury is counterproductive. Inflammation can turn into an unnecessary attack on the body's own tissues, as in arthritis or autoimmune disease. There is increasing evidence that inflammation accompanies the death of motor neurons in ALS. However, evidence so far does not support that ALS is an autoimmune disease. The inflammatory process apparently is a reaction to the death of the cells, and not the instigator.

The glia cells that usually support and nourish their neighboring neurons in the nervous system can become over active in certain diseases. Researchers think the glia act as part of the immune system. But if the glia become too activated, they can produce unwanted effects and perhaps add to the damage.

Signals of Inflammation

Cytokines are small proteins released by white blood cells to signal to other parts of the immune system. In the brain and other nervous tissues, the cytokines communicate between neurons, astrocytes (one of the major types of glia) and microglia (a second type of glial cell). An important mediator of inflammation, even in the brain, is the cytokine called tumor necrosis factor alpha (TNFa). This cytokine is meanwhile regulated by other metabolic pathways involved in inflammation.

Aspirin and other anti-inflammatory drugs interrupt the process of inflammation by inhibiting the enzyme known as cyclooxygenase. Some drugs are now available that are specific for a particular cyclooxygenase, called COX2. Animal experiments have suggested that COX2 inhibitors might be of use in ALS, but a clinical trial of a direct inhibitor of COX2 has failed to give a definitive answer. Other places in the inflammatory cascade of events might be interrupted by drug action that could help in ALS. Research in the field seeks new ways to implement an anti-inflammatory strategy in treating ALS