Genetic variants mimicking IL-6 inhibition linked to lower cardiovascular risk

People with lower interleukin-6 activity have a reduced risk of cardiovascular diseases, a new LMU study reveals.

Lowering the activity of interleukin-6 (IL-6) - a key immune signal regulating inflammatory responses in the body - could reduce the risk of cardiovascular disease without making people more vulnerable to infections, according to new research from LMU's Institute for Stroke and Dementia Research and international collaborators.

The team led by Dr. Marios Georgakis, Junior Group Leader at the Institute for Stroke and Dementia Research (ISD) and member of the SyNergy cluster of excellence, used large-scale human genetic analyses to mimic the effects of drugs that block IL-6. Previous genetic studies had focused on variants in the IL6R gene, which encodes not IL-6 itself but the corresponding receptor. "These studies suggested that suppressing the IL-6 receptor could be associated with cardiovascular benefits, but raised concerns about increased infection risk," explains Georgakis. Whether these findings would translate to under-development drugs that directly inhibit IL-6 remained unclear. And so the LMU researchers turned their attention to genes that encode IL-6.

In the new study, published in Nature Cardiovascular Research, they analyzed genetic data from over half a million people of European and East Asian ancestry. They found that individuals carrying variants in the IL6 gene linked to lower IL-6 signaling had a reduced lifetime risk of coronary heart disease, stroke, and peripheral artery disease. Strikingly, these variants were also associated with a lower risk of pneumonia and sepsis - countering fears that blocking IL-6 might impair the body's ability to fight infections.

Our study shows that genetic variants mimicking IL-6 inhibition are associated with lower cardiovascular risk and, potentially, even a lower risk of specific infections."

Lanyue Zhang, first author of the paper

"Our findings highlight how human genetics can be used to anticipate the benefits and risks of new therapies. The results support both the efficacy and safety potential of under-development IL-6 inhibitors currently in clinical trials for cardiovascular disease," says Georgakis. The genetic evidence also pointed to potential improvements in type 2 diabetes risk and lipid profiles, hinting at broader metabolic benefits.