Researchers from Washington University School of Medicine in St. Louis have discovered that a particular type of immune cell encourages harmful inflammation in the heart after a heart attack, and they have found a potential solution for protecting the heart.
The study, which was led by Dr. Douglas L. Mann, showed that a mouse model of human heart attack lived longer than control mice when treated with the drug pirfenidone, a drug already approved for treating lung conditions. The researchers showed that the drug works by regulating the immune response of B cell lymphocytes in the heart, thereby reducing inflammation and progressive injury following a cardiac event.
Pirfenidone is already used to treat idiopathic pulmonary fibrosis, a condition in which the lungs become increasingly damaged and form scar tissue rather than healthy, functioning tissue. The researchers hope to understand how pirfenidone works in the heart and reduces inflammation; in doing so, they could potentially modify the drug to work more efficiently.
The drug is already approved by the FDA and was known to protect the heart due to a number of other studies in animal models of heart attack. Researchers had previously assumed that pirfenidone protected the heart by slowing the formation of scar tissue, which is the same way that it protects lungs. However, the discovery that it helps the heart by modulating the activity of B cell lymphocytes is new and unexpected.
In this study, pirfenidone did not reduce the formation of scar tissue in the heart, but it did reduce inflammation. The researchers looked at various types of immune cells in the heart, such as macrophages, T cells, neutrophils, and monocytes, but no changes in these cells had been seen following a heart attack in mice, whether they were given pirfenidone or not. However, when the researchers examined B cells, they were surprised by a massive difference.
The results showed that B cells were, in fact, playing a key role in heart inflammation, which was unexpected. The team also discovered that there is not just one type of B cell in the heart; there are, in fact, many different types, and pirfenidone modulates these cells to reduce inflammation and protect the heart from further injury after a heart attack.
When the researchers removed the B cells completely from the heart, the heart was not protected, and the drug also had no beneficial effect. This suggests that the B cells can be either harmful or protective, depending on their activity, and this is consistent with other studies that modulate immune cells. The protective effects of the drug are dependent on the presence of B cells; if this were not the case, removing them would also protect the heart, and it does not.
Pirfenidone modulates the activity of these B cells, thus altering their behavior so that they become protective; these cells may also influence other cell types, and the researchers are now trying to find out exactly how. They are hoping to work out exactly how pirfenidone works so that they might improve it and reduce its side effects; now that they know that B cells are the drug’s target, they can begin to refine it.
We have seen a number of other studies showing that modulating the immune response to manage unwanted inflammation leads to better outcomes, and this B cell study further confirms this fact. The immune system is a key player in why we age, and the more we understand it and manage inflammation, the better we will become at inducing regeneration and repair.
 Adamo, L., Staloch, L. J., Rocha-Resende, C., Matkovich, S. J., Jiang, W., Bajpai, G., … & Bhattacharya, D. (2018). Modulation of subsets of cardiac B lymphocytes improves cardiac function after acute injury. JCI insight, 3(11).