Inflammation is a natural process that occurs as the immune system responds to an injury or infection in the body. In most cases, inflammation helps to promote healing.

But in some cases, inflammatory processes can go awry, attacking healthy cells and tissues in the body, interrupting the normal functioning of systems, and increasing the risk of other illnesses.

Clinicians are good at identifying patients with signs of inflammation, but have little guidance on whether the process is being helpful or harmful. It is tough to know whether to stand back and let the body heal itself or to intervene.

Now, a new study led by researchers at Massachusetts General Hospital (MGH) and Harvard Medical School (HMS) has identified two biomarkers in the blood that can help to tell if inflammation is helpful or harmful.

The study, which was led by John Higgins, MD, of the Center for Systems Biology and the Department of Pathology at Mass General, was recently published in Nature Communications and highlighted in a Harvard Medical School press release.

Here are five things to know:

The researchers first looked at medical record data from ~4,700 patients who had undergone non-emergency cardiovascular (CV) surgical procedures such as coronary bypass or valve replacement. All CV surgery prompts an inflammatory response due to the tissue damage and trauma that occurs in accessing the heart.

By analyzing dozens of measures simultaneously, the team identified patterns that reliably identified which patients were on track for recovery. They then narrowed their findings down to changes in two variables —white blood cell count and platelet count.

White blood cell production increases during inflammation to destroy infected cells and help direct other immune responses. Platelet count initially decreases as the platelets are used to help with clotting, then starts to increase again as the body recovers.

Among the patients who recovered well after surgery, white blood cell count decreased at a precise rate, while platelet count increased at a different–but also precise–rate. These trajectories, the researchers said, can be used to monitor recovery in a personalized way.

The team then looked at other types of surgery that cause significant inflammation, including hip replacements and limb amputations. They also looked at data from patients who had experienced heart attacks, inflammation-causing infections such as COVID-19 and C. difficile, and sepsis—a life-threatening inflammatory response.

Once again, the patients who recovered well followed the same trajectories in terms of decreasing white blood cells and increasing platelet counts.

“What is exciting about this study is that it suggests there are common features of the recovery path for a surprisingly wide range of diseases, says Higgins, who is a Pathologist at MGH and also a Professor of Systems Biology at HMS. “And if we know what a good recovery looks like, then we should be able to identify a bad one.”

The researchers are now hoping to shift their focus to earlier on in the recovery process to see if they can identify indications of a good inflammatory response during the initial development of inflammation.

This could help in identifying at-risk patients earlier on in the recovery process and in designing interventions that improve outcomes.

Additional co-authors of the paper include Brody Foy, DPhil, of the Center for Systems Biology and Department of Pathology, Thoralf Sundt, MD, chief of the Division of Cardiac Surgery and Director of the Corrigan Minehan Heart Center at Mass General, Jonathan Carlson, MD, PhD, from the Center for Systems Biology and the Mass General Cancer Center, and Aaron Aguirre, MD, PhD, from the Center for Systems Biology and the Division of Cardiology.

About the Mass General Research Institute
Research at Massachusetts General Hospital is interwoven through more than 30 different departments, centers and institutes. Our research includes fundamental, lab-based science; clinical trials to test new drugs, devices and diagnostic tools; and community and population-based research to improve health outcomes across populations and eliminate disparities in care.
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