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Statins could be useful in organ transplantation

Abi Berger, BMJ

Statins have an effect on the immune system that is completely independent of their conventional use in reducing cholesterol levels.

Scientists in Switzerland have elucidated the mechanism by which statins seem able to confer benefit on patients receiving heart transplants. Their observations may lead to a reduction in the heavy use of potent drugs such as cyclosporin for all transplant patients (Nature Medicine 2000;6:1399-402).

Whereas the beneficial effects of statins on lipids in the cardiovascular system are well known, it is also becoming clear that statins can influence the immune system. When it was first observed, in 1995, that giving statins to heart transplant patients improved their survival rates compared with treatment with placebo, it was put down to the lipid lowering effects of the drugs, but it is now thought that the drugs also modulate the immune system.

Dr François Mach, associate professor of medicine, and his colleagues at Geneva Medical School, have reported the hitherto undetected anti-inflammatory effects of statins using an in vitro model.

Their model suggests that statins shut down the alarm systems usually present on antigen presenting cells, making foreign tissues less likely to trigger an immune response against them. The statin mechanism involves the expression of major histocompatibility complex class II (MHC-II) molecules. MHC-II cells are responsible for presenting foreign antigens on the surface of immune cells.

Dr Mach's team have discovered that, although statins do not influence the basic expression of MHC-II molecules, they do seem to be able to repress the MHC-II molecules that are induced by foreign tissue. They do this by blocking the ability of interferon gamma, a cytokine, which activates antigen presenting cells to express MHC-II on their surface.

"This is more of an immune repression, rather than immune suppression," explains Dr Mach. "It doesn't necessarily mean we can expect to replace cyclosporin with a statin, but we may be able to use statins to reduce the dose of cyclosporin that is needed." Statins have far fewer and much milder side effects than cyclosporin.