Heart-disease drugs called statins were designed to lower the body's production of cholesterol, but they also help heart patients by reducing inflammation--a surprise benefit that delighted but also puzzled researchers. Now a team has pinpointed where in the immune system statins block inflammation. Eventually, statins might be used to prevent the rejection of transplanted organs or ease symptoms of autoimmune disorders.
Statins have a wide range of effects. Earlier this year, researchers suggested that these drugs reduce the risk of Alzheimer's disease (ScienceNOW, 13 November) and build bone mass (ScienceNOW, 27 June). One of the first clues that the drugs might also calm the immune system came from a 1995 study of heart transplant patients. Patients who took statins showed fewer signs of rejecting the transplanted organ.
To investigate, cardiologist François Mach of the Geneva Medical School in Switzerland and colleagues focused on inflammation in blood vessels. When the immune system triggers this inflammation, it can lead to transplant rejection--and may aggravate heart disease. The researchers traced the effects of statins on cells from the inner wall of blood vessels when they were combined with several types of immune cells. They found that statins block a chemical messenger that activates a kind of white blood cell called a T lymphocyte. This slows the cascade of cellular interactions that normally causes the kind of inflammation that leads to transplant rejection, they report in the December issue of Nature Medicine.
Mach points out that his research might have applications for autoimmune diseases as well, some of which involve T lymphocytes gone haywire. His team plans to test whether statins can prevent a rheumatoid arthritis-like disease in mice.
The finding that statins block T lymphocyte activation is "a tremendous confirmation [that statins] have cholesterol-independent properties by which they can save lives, " says cardiologist Jon Kobashigawa of the University of California, Los Angeles, who conducted the 1995 heart transplant study. But Wulf Palinski, an atherosclerosis specialist at the University of California, San Diego, cautions that what works in cell culture may not work in a live animal. "The immune system is hugely complicated, " he says.