Immunosuppressive cell and cytokine response linked to bone nonunion

February 17, 2021

EUGENE, Ore. -- Feb. 18, 2021 -- An abnormal suppression of the immune system linked to the onset of numerous diseases has been associated with poor functional regeneration of traumatic bone injuries.

Levels of immune cells and proteins circulating in the blood following traumatic injury combined with advanced data analytics could predict whether patients are likely to respond to treatment, said Robert Guldberg, executive director of the Phil and Penny Knight Campus for Accelerating Scientific Impact.

The project -- detailed in a paper published online ahead of print in the Proceedings of the National Academy of Sciences -- identified myeloid-derived suppressor cells and the immunosuppressive cytokine IL-10 as the strongest predictors of delayed and less effective bone-healing.

That association emerged after a series of experiments in which Guldberg's team ran thousands of data models on hundreds of biomarkers.

Guldberg was the principal investigator on the research, which was supported by the U.S. Armed Forces Institute of Regenerative Medicine and done with colleagues at Georgia Tech and Evolved Analytics.

"Our studies showed that myeloid-derived suppressor cells were consistently elevated in the blood as well as the local tissue in the non-responders to treatment, suggesting that suppression of the immune system may negatively affect musculoskeletal healing," Guldberg said. "That opens up potential novel therapeutic targets to improve patient outcomes following traumatic injuries."

Although standard bone fractures heal 95 percent of the time, complex fractures or trauma that cause damage to bones and surrounding soft tissues such as muscle have higher rates of complications and often require multiple procedures to heal. These non-healing bones are referred to as being in nonunion.

Factors such as age or underlying conditions, Guldberg said, can increase the risk of complications, motivating the need for biomarkers that can predict patient outcomes.

"We were quite intrigued to identify biomarkers that could be measured from the blood that correlated with local healing," he said. "The observation that was most exciting though was that immunosuppressive biomarkers were elevated as early as one week after treatment, well before radiographs could be used to assess the progress of healing."

A similar dysregulated immune response is seen in early stages of infections, cancer and other diseases. Myeloid-derived suppressor cells normally activate along with other cell groups that respond to injury or a pathological condition. In turn, various proteins, such as the cytokines identified in the new paper, activate to control inflammation. Under normal conditions following injury, these compensatory responses return to normal levels.

When that compensation fails to occur, Guldberg said, patients can enter a state of chronic inflammation and sustained immune suppression that appear to be associated with poor treatment outcomes.

Under a recently awarded 2.5 million, five-year grant from the National Institutes of Health, Guldberg will lead a team to further characterize and confirm the immune biomarkers in anticipation of a possible human clinical trial and test a new immunomodulation treatment strategy.
-end-
Co-authors with Guldberg on the PNAS paper were Georgia Tech doctoral students Albert Cheng and Casey E. Vantucci, the study's lead authors, former Georgia Tech doctoral student Marissa A. Ruehle and Georgia Tech researchers Laxminarayanan Krishnan, Levi B. Wood and Krishnendu Roy, and Theresa Kotanchek of Evolved Analytics.

Links

Phil and Penny Knight Campus for Accelerating Scientific Impact: https://accelerate.uoregon.edu/

About Robert Guldberg: https://accelerate.uoregon.edu/robert-guldberg

Guldberg Lab: https://guldberg.uoregon.edu/

NIH grant Immunoengineering Strategies for Musculoskeletal Trauma: https://reporter.nih.gov/search/3N98srihc0aNp3vymzsUiw/project-details/9974169

University of Oregon

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.