Influenza Triggers Immune Responses Resulting in Relapse in Patients with Multiple Sclerosis

Influenza, is a contagious respiratory illness that places a substantial burden on the health of individuals in the United States every year. The Centers for Disease Control and Prevention estimates that influenza is responsible for a staggering 9.2 million to 35.6 million illnesses, between 140,000 and 710,000 hospitalizations, and between 12,000 and 56,000 deaths every year since 2010.

Furthermore, it has been found that the common flu causes more harm to individuals with multiple sclerosis (MS) and other neurological conditions than those without, because the virus can trigger a multitude of immune responses that result in relapse.

In fact, in a study published in the Proceedings of the National Academy of Sciences, investigators sought to determine what causes relapse and to gain insight into brain activity of patients with MS during upper respiratory infections.

“We know that when MS patients get upper respiratory infections, they’re at risk for relapse, but how that happens is not completely understood,” said author Andrew Steelman, PhD, assistant professor with appointments in the Department of Animal Sciences, the Neuroscience Program, and the Division of Nutritional Sciences at the University of Illinois College of Agricultural, Consumer, and Environmental Sciences in a recent press release. “A huge question is what causes relapse, and why immune cells all of a sudden want to go to the brain. Why don’t they go to the toe?”

For the study, the investigators used a strain of laboratory mice genetically prone to develop an autoimmune attack of the brain and spinal cord. Once the mice were exposed to influenza, the investigators examined changes in their brains.

The findings showed flu exposure induced MS-like symptoms in some of the mice, even though the virus was not found in the brain, the authors wrote.

“If you look at a population of MS patients that have symptoms of upper respiratory disease, between 27% and 42% will relapse within the first week or 2.” Dr. Steelman said. “That’s actually the same incidence and timeframe we saw in our infected mice, although we thought it would be much higher given that most of the immune cells in this mouse strain are capable of attacking the brain.”

Upon closer investigation, the findings showed an increase in glial activation in the brains of mice infected with influenza.

“When glia become activated, your start to see trafficking of immune cells from the blood to the brain,” Dr. Steelman explained. “We think that, at least for MS patients, when glia become activated this is one of the initial triggers that causes immune cells to traffic to the brain. Once there, the immune cells attack myelin, the fatty sheaths surrounding axons, causing neurologic dysfunction.”

The investigators hypothesize that glia may send signals to immune cells via chemokines. One chemokine, CXCL5, had elevated levels in the brains of mice infected with the flu, as well as in the cerebral spinal fluid of patients with MS during relapse. To further strengthen these findings, other scientists recently suggested CXCL5 could be used to predict relapse.

Although the findings provide further insight into how immune cells are signaled to the brain during an upper respiratory infection, the investigators remain unsure of why the immune system attacks the brain.

“MS patients have 1 or 2 relapses a year; it’s thought that these relapses contribute to the progression of the disease,” Dr. Steelman said. “If we can pinpoint what’s driving environmental factors such as infection to cause relapse, then maybe we can intervene when the patient has signs of sickness, like runny nose or fever. It we could inhibit relapse by 50%, we could theoretically prolong the time it takes for the patient to experience continual loss of function and dramatic disability.”