A human heart recuperating from inflammation, a condition called myocarditis, can take one of two paths: a healthy return to normal function or a dangerous transition to another condition called inflammatory dilated cardiomyopathy (DCMi). In the past scientists have been bewildered as to why some people recover and others do not, but a recent study’s findings shows that the presence of a certain type of immune cell may be the explanation.
"Our studies show that the presence of eosinophils in the heart makes mice more likely to get DCMi following myocarditis,” explained first author of a new study published in The Journal of Experimental Medicine, Nicola Diny. “And if there are a lot of eosinophils, the mice develop even more severe heart failure.”
Eosinophils are white blood cells with specific “instructions” from the immune system to fight parasites, and they are also linked to allergies, autoimmune disease, and some types of cancer. Myocarditis is under-studied and probably under-diagnosed as a result. A myocarditis diagnosis requires a biopsy to be taken directly from a person’s heart tissue. On the rare occasions when it is diagnosed, the specific type of myocarditis is identified by the most prevalent type of immune cell present in the heart.
Following coronary artery disease and arterial hypertension, dilated cardiomyopathy is a top cause of heart failure. DCMi is one of many types of dilated cardiomyopathy, all of which are characterized by a dysfunctional heart muscle.
Connections have already been made between high levels of eosinophils and the development of heart disease, but the present study, led by senior author Daniela Cihakova, MD, PhD, is the first to examine eosinophil activity through the lens of heart inflammation. The new research, Cihakova said, “provided more details about how these immune system cells may lead to deterioration of heart muscle function in mice in a way that lets us draw some parallels to human disease processes.”
To definitively confirm the role of eosinophils in the progression of myocarditis to DCMi, Cihakova designed a classic study: a comparison between normal mice and mice genetically altered to lack eosinophils. After both groups were induced to have myocarditis, Cihakova looked for inflammatory patterns.
There were similar levels of initial, acute inflammation in the heart in both groups of mice. However, as more time passed, the difference in the long-term effects between the two groups of mice grew remarkably distinct; normal mice developed heart failure and mice lacking eosinophils did not.
"The take-home message is that inflammation severity doesn't necessarily determine long-term disease progression,” Cihakova explained. “But specific infiltrating cell types - eosinophils, in this case - do.”