The team led by study leader Dr. Marios Georgakis, junior group leader at the Institute for Stroke and Dementia Research (ISD) and member of the SyNergy Cluster of Excellence, used extensive human genetic analyses to mimic the effect of drugs that block IL-6. Earlier genetic studies had focused on variants of the IL6R gene, which does not code for IL-6 itself, but the associated receptor. "This work suggested that cardiovascular benefits could be associated with inhibition of the IL-6 receptor, but had raised concerns about an increased risk of infection," explains Georgakis. Whether these results could be applied to drugs under development that directly inhibit IL-6 remained unclear. For this reason, the researchers at LMU Hospital have now turned their attention to genes that code for IL-6.

In the new study, which was published in the journal Nature Cardiovascular Research, they analyzed genetic data from over half a million people of European and East Asian descent. They found that individuals with variants in the IL-6 gene associated with lower IL-6 signaling had a lower risk of coronary heart disease, stroke and peripheral artery disease over their lifetime. Remarkably, these variants were also associated with a lower risk of pneumonia and sepsis - invalidating fears that blocking IL-6 could impair the body's ability to fight infection.

"Our study shows that genetic variants leading to IL-6 inhibition are associated with lower cardiovascular risk and possibly even lower risk of certain infections," says Lanyue Zhang, first author of the study. "Our results demonstrate how human genetics can be used to predict the benefits and risks of new therapies. The study highlights the potential of effective and safe IL-6 inhibitors currently being developed in clinical trials for cardiovascular disease," says Georgakis. The genetic evidence also suggests possible improvements in the risk of type 2 diabetes and lipid profile, suggesting wider metabolic benefits.