Resolving Chronic Inflammation
Many chronic inflammatory diseases are related to a reduction or absence of specialized pro-resolving mediators.
Recent studies highlight the significance of addressing the damage caused by acute inflammation alongside the initial inflammatory response. In a National Geographic Science Newsletter, Ruslan Medzhitov, PhD, a professor of Immunology at Yale School of Medicine stated, “Simply stopping inflammation is not enough to return tissue to its normal state.”1
It was once assumed that acute inflammation ceased spontaneously, and it was presumed that the dead tissues resulting from this process were eventually metabolized. This has been demonstrated not to be true in many cases; the result is chronic inflammation. This finding has led to an increased emphasis on ensuring a transition from the acute inflammation to repair, avoiding the problems created by chronic inflammation.
Ruslan Medzhitov, PhD, a professor of immunobiology at Yale School of Medicine, compares an acute infection to flooding seen after a water pipe breaks. Once the water recedes, residual damage must be removed. This repair is initiated by signaling molecules called specialized pro-resolving mediators (SPMs).
SPMs have proved to be difficult to study in the laboratory. To overcome this problem Catherine Godson, PhD, a professor of molecular medicine at University College Dublin, studies synthetic versions of these lipid derivatives on diabetic mice and tissue from patients with atherosclerosis. In both cases, these synthetic versions reversed the disease process.
A great deal of data exist on how these molecules affect the actions of macrophages. This is important because macrophages are responsible not only for the acute phase of inflammation but they also contribute to either chronicity or repair of the inflammatory process.
It is now suggested that once the acute disease is over, SPMs signal macrophages to clean up damaged tissue by releasing signals that encourage proliferation and repair. Many chronic inflammatory diseases are related to a reduction or absence of SPMs, which can block the macrophages’ ability to phagocytize debris, thus locking the body into a chronic inflammatory state.
This may be one of the reasons why COVID-19 is more severe in older individuals. Another hypothesis is that toxins, growth factors, and other inflammatory byproducts enhance the growth of certain cancers. Some conventional treatments for cancer may exacerbate the problem, according to Dipak Panigrahy, MD, an assistant professor of pathology at Beth Israel Deaconess Medical Center. He says that traditional chemotherapy and radiation kill the tumor but leave debris that needs to be cleared up for the chronic inflammation to resolve. Currently his laboratory is working with one of the pro-inflammatory mediators in phase 1 clinical trials for pancreatic, brain, and colon cancers. SPMs are also currently being tested for their effect on chronic periodontal diseases.
Thomas G. Wilson Jr., DDS
Editor in Chief
- Chang C. The end of inflammation? New approach could treat dozens of diseases. National Geographic Science Newsletter. March 6, 2022.
From Decisions of Dentistry. October 2023; 9(9):6