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Immune System Protein May Protect Against Diabetes

GAINESVILLE — January 8, 1998 — Researchers at Harvard University and the University of Florida have identified a component of the human immune system that appears to prevent diabetes in a group of people considered highly likely to contract the disease.

The substance, a naturally occurring protein manufactured in large amounts in these individuals, is known as interleukin-4, or IL-4, researchers report in the Jan. 8 issue of the journal Nature. Insulin-dependent, or Type I, diabetes occurs when white blood cells vital to the body’s defenses against infectious diseases launch a self-directed, or autoimmune, attack on insulin-producing beta cells in the pancreas. The insulin these beta cells produce regulates how the body uses and stores sugar and other food nutrients for energy.

“The presence of this protein, IL-4, may suppress the arm of the immune system involved in the destruction of insulin-producing cells,” said Mark Atkinson, director of UF’s Center for Immunology and Transplantation. “By producing this large amount of IL-4, these people–though they have an autoimmune event going on within their bodies–seem to be prevented from developing diabetes.”

Researchers, funded by the federal National Institutes of Health, studied 11 people–including identical twins and triplets with and without diabetes, and normal controls–to hunt for the white blood cells that make IL-4 and also may regulate the ability of other cells to manufacture it. They also took blood samples from more than 180 patients to measure IL-4 levels.

Researchers tracked participants for an average of nine years; some were monitored for as long as 20 or 30.

“More than 50 percent of these individuals should have gone on to develop autoimmune (insulin-dependent) diabetes during a five-year follow-up period,” said Dr. Brian Wilson, who at the time of the study was a postdoctoral fellow in the department of molecular and cellular biology at Harvard. Wilson, now affiliated with the department of tumor virology at the Dana Farber Cancer Institute at Harvard Medical School, collaborated with other Harvard researchers as well as the diabetes research group at UF. But half the people who should have developed diabetes didn’t, Wilson said.

“If we looked across the board at twins who did not develop diabetes, all the T cells [white blood cells] of this regulatory ilk were making huge amounts of IL-4,” Wilson said. “When we looked at the genetically identical twin who had type 1 diabetes, there was an absolute absence of the ability to make IL-4, and in fact, they made boatloads of an inflammatory agent.”

Why some people at high risk of developing diabetes don’t get it–even though they test positive for so-called autoantibodies, which signal the body’s assault on pancreatic beta cells is under way, long before symptoms appear–has long puzzled scientists.

“These people have these autoantibodies but don’t ever go on to develop diabetes–and it’s always been a great mystery why,” Atkinson said. “We think we’ve discovered a potential answer. The big question now is whether there is a way to take advantage of the situation so other autoantibody-positive people who don’t make massive amounts of interleukin-4 don’t develop the disease.”

More than 16 million Americans have diabetes. At least 150,000 die annually as a result of the disease and its complications, which include heart disease, stroke, blindness, kidney failure and poor circulation to the lower limbs.

UF and Harvard researchers are conducting a follow-up study of 69 families–about 450 people–that will further examine IL-4’s protective role and whether its production is a genetic trait, Atkinson said.