Researchers may be closer to understanding why the flu can prompt relapses for patients with multiple sclerosis.
Multiple sclerosis (MS) is a chronic disease triggered by an abnormal immune response, wherein the immune system mistakingly attacks and damages myelin, which is the fatty substance that protects nerve fibers in the central nervous system.
When myelin is attacked, the underlying nerve fibers may also be damaged. This interferes with nerve signaling between the brain and spinal cord, causing symptoms such as numbness or tingling in face, body, or limbs, muscle weakness, and mobility difficulties.
Relapsing-remitting MS is the most common form of MS, and it is characterized by attacks of symptoms, or relapses, followed by periods of recovery.
Previous research has found that flu and other upper respiratory infections may increase the risk of relapse in patients with MS. The mechanisms underlying this association, however, have been unclear.
Prof. Andrew Steelman, of the University of Illinois at Urbana-Champaign, and colleagues sought to learn more about the link between flu and MS relapse.
For their study - which has recently been published in the Proceedings of the National Academy of Sciences - the researchers used mice that were genetically susceptible to immune-mediated attacks of the brain and spinal cord.
Flu increased glial cell activation
The researchers exposed the mice to the influenza A virus, which is a primary cause of flu epidemics in humans. The rodents' response to the virus was monitored.
The team found that some of the infected mice initially developed symptoms similar to those seen in humans with MS, even though there were no traces of the flu virus in the rodents' brains.
"If you look at a population of MS patients that have symptoms of upper respiratory disease, between 27 and 42 percent will relapse within the first week or two," notes Prof. Steelman.
"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."
Interestingly, when the researchers took at closer look at the brains of the flu-infected mice, they identified an increase in the activation of glial cells.
While a main role of glial cells is to support neurons in the central nervous system, studies have shown that glial cells also help to summon immune cells to the brain.
"When glia become activated, you start to see trafficking of immune cells from the blood to the brain. 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," explains Prof. Steelman.
"Once there, the immune cells attack myelin, the fatty sheaths surrounding axons, causing neurologic dysfunction," he adds.
Chemokines may be involved
The researchers hypothesize that molecules called chemokines mediate the signaling between glial cells and immune cells, after identifying increased levels of a chemokine called CXCL5 in the brains of flu-infected mice.
What is more, the team notes that in humans with MS, CXCL5 levels are increased in cerebral spinal fluid during relapses, and recent research suggests that this chemokine could be used to predict MS relapse.
While further studies are needed to pinpoint precisely why the immune system of MS patients attacks the brain in response to upper respiratory infections, Prof. Steelman and team believe that their study brings us one step closer to finding out.
"MS patients have one or two relapses a year; it's thought that these relapses contribute to the progression of the disease," says Prof. Steelman. "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."
"If we could inhibit relapse by 50 percent, we could theoretically prolong the time it takes for the patient to experience continual loss of function and dramatic disability."
Prof. Andrew Steelman