Severe inflammation in the lungs can become life-threatening very quickly.
Researchers at the University at Buffalo are exploring whether an omega-3 fatty acid found in foods such as salmon could be turned into a new treatment for dangerous lung injury.
The work focuses on acute respiratory distress syndrome, or ARDS. This condition can develop after pneumonia, severe infections, COVID-19 and other illnesses damage the lungs and trigger an extreme immune response.
In ARDS, the tiny air sacs that normally move oxygen into the blood can fill with fluid. As breathing becomes harder, patients may need intensive care and mechanical ventilation to keep enough oxygen moving through the body.
ARDS affects more than 200,000 people each year in the United States, according to University at Buffalo researcher Zhenjia Wang. He says about 30% to 50% of patients die, showing why better treatments are urgently needed.
Current care mainly supports patients while their lungs recover. Doctors may use ventilators, manage fluid levels and give anti-inflammatory medicines such as steroids, but these treatments do not work equally well for everyone.
Suppressing inflammation can also create a difficult balance. The immune system causes some of the lung damage, but patients still need that same immune system to fight the infection that may have triggered the illness.
Wang, a professor in the University at Buffalo School of Pharmacy and Pharmaceutical Sciences, recently received a $2 million, four-year grant from the National Heart, Lung, and Blood Institute. He is working with immunologist Elsa Bou Ghanem from UB’s Jacobs School of Medicine and Biomedical Sciences.
Their research centers on neutrophils, a common type of white blood cell. These cells are among the body’s first responders to infection, but when too many gather in the lungs and remain highly active, they can contribute to damaging inflammation.
Instead of simply blocking neutrophils, the researchers want to use them to help calm the inflammatory response. Their approach begins with DHA, an omega-3 fatty acid found in fatty fish and fish-oil products.
The body can convert DHA into molecules known as resolvins. These molecules help bring inflammation to an end while supporting tissue repair and allowing the immune system to continue protecting the body from infection.
Two resolvins, called RvD1 and RvD2, have shown promise in laboratory research. However, turning resolvins themselves into practical medicines has been difficult because the compounds can be unstable.
The UB team is trying a different approach. Rather than delivering finished resolvins, they plan to send DHA directly into neutrophils in inflamed lung blood vessels and let the cells produce the helpful molecules where they are needed.
To do this, the scientists will package DHA inside tiny fat-based particles called liposomes. These particles are designed to carry substances through the body and can potentially be engineered to deliver their contents to particular cells.
Once DHA enters the targeted neutrophils, enzymes inside the cells may convert it into inflammation-resolving molecules. In theory, the lungs could then become a small biological factory producing resolvins directly at the site of injury.
The researchers will first design and test liposomes that can efficiently deliver DHA to neutrophils. They will then examine whether treated cells produce more resolvins and whether the approach reduces lung damage in mouse models of acute lung injury.
The project is supported by a four-year National Heart, Lung, and Blood Institute grant from the U.S. National Institutes of Health and is being conducted at the University at Buffalo. The work is currently preclinical research, meaning the proposed treatment has not yet been shown to work in people with ARDS.
The idea is scientifically interesting because it aims to guide inflammation toward a natural ending rather than simply shutting down immune activity. If successful, that difference could potentially help protect lung tissue while preserving some ability to fight infection.
However, the research remains at an early stage. Results in mice do not always translate to humans, and scientists will need to establish safety, dosing, effectiveness and reliable nanoparticle delivery before this strategy could enter routine medical care.
The broader possibility is also intriguing because neutrophils contribute to inflammation in many diseases. Wang believes the same delivery strategy might eventually be studied in conditions such as arthritis, Crohn’s disease and autoimmune disorders, but those applications remain future possibilities rather than proven treatments.
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Source: University at Buffalo.
