Newly Discovered Immune Response Could Benefit Treatment of Spinal Cord and Brain Injuries

In a discovery that could benefit the treatment of spinal cord and brain injuries, researchers at the University of Virginia and elsewhere have identified a previously unknown, beneficial immune response that occurs after injury to the central nervous system.

By harnessing this response, doctors may be able to develop new and better treatments for brain and spinal cord injuries, develop tools to predict how patients will respond to treatment, and better treat degenerative conditions such as multiple sclerosis, Alzheimer’s disease, glaucoma and Lou Gehrig’s disease, according to the researchers, whose work is published in the Journal of Clinical Investigation.

The newly discovered immune response occurs independently of the process that typically stimulates the immune system into action. In that process, the body identifies and attacks substances known as antigens, such as bacteria and viruses.

“What we have shown is that the injured central nervous system talks to the immune system in a language that hasn’t been previously recognized in this context,” said Jonathan Kipnis, a professor in the Department of Neuroscience at University of Virginia’s School of Medicine and director of the Center for Brain Immunology and Glia. “It sends ‘danger signals’ and activates the immune system very rapidly. These danger signals cause immune cells to produce a molecule called interleukin 4 (IL-4), which happens to be indispensable for immune-mediated neuroprotection after (central nervous system) trauma.”

The body’s immune system is a person’s primary defense against disease, infection and foreign substances. When cells die as a result of trauma, the immune system is activated to remove the dead cells and other debris. Inflammation of the damaged area is part of the immune system response, but inflammation after traumatic spinal cord injury can lead to damage to the healthy cells of the nervous system, explained Edelle Field-Fote, PT, Ph.D., director of spinal cord injury research at Shepherd Center in Atlanta.

“This University of Virginia study (1) builds on earlier studies that showed the immune system’s T-cells help protect the nervous system after spinal cord injury,” Dr. Field-Fote said. “The researchers were able to identify IL-4 as the specific substance produced by the immune system that is responsible for this protective effect. Unlike some of the substances that accompany trauma, IL-4 is an anti-inflammatory substance, so it decreases rather than increases inflammation.”

Earlier studies also show the benefits of IL-4, Dr. Field-Fote noted. A 2010 study (2) in animal models of spinal cord injury showed that IL-4 not only reduces inflammation, but also helps to reduce the formation of cavities within the damaged spinal cord. And a 2011 article (3) reviewed the available research and concluded that IL-4 seems to support natural processes that promote growth and repair after spinal cord injury.

“All in all, there seems to be exciting progress in the evidence showing that IL-4 may be a substance that can contribute to the goal of reducing damage to the nervous system after spinal cord injury,” Dr. Field-Fote said. “IL-4 definitely deserves further study.”

To read more about the University of Virginia study, click here.

For additional reading, see the following journal articles that Dr. Field-Fote cited:

1. Walsh JT et al. MHCII-independent CD4+ T cells protect injured CNS neurons via IL-4. J Clin Invest. 2015 Jan 20. pii: 76210.

1. Lee SI et al. Endogenous expression of interleukin-4 regulates macrophage activation and confines cavity formation after traumatic spinal cord injury. J Neurosci Res. 2010;88(11):2409-19.

1. David S, Kroner A. Repertoire of microglial and macrophage responses after spinal cord injury. Nat Rev Neurosci. 2011; 12:388–399, doi:10.1038/nrn3053, pmid:21673720.

For more information on Shepherd Center research, click here.