Study shows IL-4 protein prevents diabetes
Discovery could be clue to disease's progression
For two decades, scientists have known that diabetes is an autoimmune disease in which the immune system, which normally defends the body, self-destructs, killing off insulin-producing cells. They've also found some ways to predict which people will develop diabetes based on genetic markers. What they haven't known is how some people with those markers, or autoantibodies, manage to avoid ever developing the symptoms of diabetes.
Now, researchers have found a potential answer to the mystery. It's called interleukin-4 (IL-4), a naturally occurring protein that appears to prevent diabetes by suppressing the arm of the immune system that destructs insulin-producing cells. A study1 published recently in Nature followed 200 people who had the autoantibodies that signal the assault on insulin-producing cells is under way. Fifteen of those people were found to be producing large amounts - as much as 100 times more than an average person - of IL-4, and they had not developed symptoms of diabetes in a five-year period.
"If a person has a relative with autoimmune diabetes, we could look at their blood for the presence of antibodies and could give that person a relatively good probability of their risk for developing diabetes based on population studies," says Brian Wilson, MD, PhD, lead author of the study and instructor in medicine at Massachusetts General Hospital in Boston. "But predictive tests are by no means certain, and as soon as you get down to the individual, they fall apart. We wanted to find why it was that certain people whom we would have predicted would have gone on to develop autoimmune diabetes did not."
The immune system is keyed up to handle insults, Wilson says, but every time it gets keyed up, there has to be a way to turn it off. "The problem is that the immune system has to be able to recognize self from non-self," he says. "What we think we're looking at is one of the mechanisms by which an immune system can stop an attack on self. If that is true, we've seen a small tip of the iceberg of what makes a competent immune system control the recognition of self."
Most of the people who have the markers do go on to develop diabetes, but there's always been a population of anywhere between 10% and 30% who continue to resist the disease, says Mark Atkinson, PhD, one of the researchers and director of the University of Florida's Center for Immunology and Transplantation. "That's been a big curiosity for us," he says. "What we're seeing is a situation where the body is putting up a defense mechanism that essentially prevents people from developing diabetes."
Now that researchers understand a potential answer to that question, they can look for clues on how to stop diabetes from progressing. "One of the things we can do now is look at people for their production of IL-4 to identify people who might be resistant to developing diabetes," Atkinson says. "This study tells us that we might need to use IL-4 as prevention or therapy for the disease. If we identify people with antibodies, they might be a good population to try and treat with IL-4."
Reference1. Wilson, et al. Extreme Th1 bias of invariant T cells in type 1 diabetes. Nature 1998; 39:177-180.
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