Immune-Suppressor Cells Affect Hypertension

Kenneth Bernstein, MD

Specialized cells that reduce inflammation play a major role in hypertension, according to a Cedars-Sinai-led study published in the American Heart Association's journal Circulation Research. Hypertension, or high blood pressure, is a serious disorder that affects nearly a third of American adults and can lead to heart attack and stroke.

The study showed, for the first time, that a build-up of myeloid-derived suppressor cells (MDSCs), which has long been associated with infections, cancer and other disorders, also occurs in hypertension. Derived from bone marrow, these cells inhibit the action of the immune system's T cells, which direct the body's inflammatory responses.

Although necessary to fight infections, inflammation can turn harmful when it becomes a chronic condition, as it often is in hypertension.

"Our study is notable because it emphasizes that inflammation plays an important role in hypertension. It also points to the complexity of the inflammatory response in a chronic disease such as hypertension," said Kenneth Bernstein, MD, director of Experimental Pathology and professor of Pathology at Cedars-Sinai. Bernstein co-authored the study along with other members of his laboratory in the Department of Biomedical Sciences.

In their study involving mice, the researchers found that in hypertensive males, MDSCs accumulated in the spleen and helped limit inflammation and increases in blood pressure. To study the process, the researchers first reduced the level of MDSCs in mice, which they found increased kidney inflammation and blood pressure. By contrast, when the level of MDSCs was increased in hypertensive mice, the animals' blood pressure went down.

The study "offers important and timely insight for the role of MDSCs in the development of hypertension," Circulation Research stated in a commentary. The results show that the immune system activates both inflammation and MDSCs, "which serve to buffer the pathological consequences of T-cell activation and the resulting hypertension," according to the commentary.

The study's authors said their data also suggest how MDSCs act on T cells: by producing chemicals known as reactive oxygen species (ROS). These chemicals can damage cells when they occur in high concentrations, as they do in the vascular tissues of hypertensive patients. But in this case, they may actually fight hypertension by helping MSDCs suppress inflammation.

This insight into the MDSC-T cell interaction has potential implications for treating patients. The researchers note that antioxidant therapy, which inhibits ROS, has been studied as an adjunct treatment for cardiovascular disease. "In such studies, it is worth considering that depletion of myeloid ROS production might exacerbate inflammation and have effects contrary to the hoped-for result," they wrote.