Scientists have identified an arthritis drug that reduces inflammation in people with West Nile virus and may help treat neurological problems persisting in patients who survive the infection.
Scientists have identified an arthritis drug that reduces inflammation in people with West Nile virus and may help treat neurological problems persisting in patients who survive the infection. “These memory disturbances make it hard for people to hold down a job, to drive, to take care of all the duties of everyday life,” said Robyn Klein, from the Washington University School of Medicine in the US. “We found that targeting the inflammation with the arthritis drug could prevent some of these problems with memory,” Klein said. Spread by the bite of a mosquito, West Nile virus can cause fever and sometimes life-threatening brain infections known as West Nile encephalitis. About half the people who survive the encephalitis are left with permanent neurological problems such as disabling fatigue, weakness, difficulty walking and memory loss. These problems not only persist but often worsen with time.
For the study published in the journal Nature Immunology, the researchers injected mice with West Nile virus or saltwater. During the acute infection, the mice received several doses of a chemical compound that tags neural cells as they are formed. Forty-five days after infection, the researchers isolated the tagged cells from the mice’s brains and assessed how many and what kinds of cells had been formed during the first week of infection. Mice ill with West Nile disease produced fewer neurons and more astrocytes – a star-shaped neural cell – than uninfected mice. Astrocytes normally provide nutrition for neurons, but the ones formed during West Nile infection behaved like immune cells, churning out an inflammatory protein known as IL-1. IL-1 is an indispensable part of the body’s immune system. Once the battle is won, the immune cells depart and IL-1 levels in the brain fall.
However, in mice recovering from West Nile infection, astrocytes continue to produce IL-1 even after the virus is gone. Since IL-1 guides precursor cells down the path towards becoming astrocytes and away from developing into neurons, a vicious cycle emerges. Astrocytes produce IL-1, which leads to more astrocytes while also preventing new neurons from arising. Hampered by an inability to grow new neurons, the brain fails to repair the neurological damage sustained during infection, the researchers said. “It’s almost like the brain gets caught in a loop that keeps IL-1 levels high and prevents it from repairing itself,” said Klein.
To see whether the cycle could be broken, the researchers infected mice with either West Nile virus or saltwater as a mock infection. Ten days later, they treated both groups of mice with a placebo or with anakinra, an arthritis drug, approved by the Food and Drug Administration (FDA), that interferes with IL-1. After giving the mice a month to recover, they tested the animals’ ability to learn and remember by placing them inside a maze. Mice that had been infected with West Nile virus and treated with a placebo took longer to learn the maze than mock-infected mice.
Mice that were infected and treated with the IL-1 blocker learned just as quickly as mock-infected mice, indicating that blocking IL-1 protected the mice from memory problems. “This study sheds light on not just post-viral memory disturbances but other types of memory disorders as well,” Klein said. “It may turn out that IL-1 is not a feasible target during viral infections, but these findings could lead to new therapeutic targets that are less problematic for clearing virus,” he added.