When severe infection reaches the lungs, the body’s attempt to fight back can sometimes become part of the problem.
Scientists at the University at Buffalo are developing an unusual strategy that could encourage immune cells inside injured lungs to produce substances that naturally help inflammation end.
The project targets acute lung injury and its more severe form, acute respiratory distress syndrome, commonly called ARDS. ARDS can follow pneumonia, COVID-19, sepsis and other serious illnesses and can leave patients unable to get enough oxygen without medical support.
Healthy lungs contain millions of tiny air sacs surrounded by small blood vessels. Oxygen normally passes through their thin walls into the bloodstream, but severe inflammation can damage this delicate barrier and allow fluid to enter the air spaces.
This makes breathing increasingly difficult and can affect organs throughout the body. Even with modern intensive care, ARDS continues to cause a large number of deaths.
Zhenjia Wang, a nanomedicine researcher at the University at Buffalo, says more than 200,000 Americans develop ARDS each year and 30% to 50% die. Current treatment is largely based on supporting breathing and controlling the underlying illness while the lungs recover.
Anti-inflammatory medicines such as steroids can sometimes help, but there is a catch. Strongly suppressing the immune response may also make it harder for the body to defend itself against secondary infections.
Wang and colleague Elsa Bou Ghanem are investigating whether inflammation can instead be encouraged to finish in a more natural way. Their work is supported by a $2 million grant over four years from the National Heart, Lung, and Blood Institute, part of the National Institutes of Health.
At the center of the project are immune cells called neutrophils. They quickly travel to areas of infection or injury and attack invading microbes, making them an essential part of the body’s early defense system.
But neutrophils can also release substances that damage surrounding tissue when their response becomes excessive or continues for too long. In ARDS, large numbers of these cells can collect in the lungs and contribute to the destructive inflammatory reaction.
The scientists want to turn these cells from part of the problem into part of the solution. They plan to deliver DHA, a well-known omega-3 fatty acid, directly into neutrophils gathered around inflamed lung blood vessels.
DHA is found naturally in fatty fish such as salmon. Inside the body, it can serve as the starting material for molecules called resolvins, which help signal that an inflammatory response should wind down.
This is different from simply blocking inflammation. Resolvins are involved in helping the body clear inflammatory material, repair damaged tissue and return toward normal while maintaining important immune defenses.
Researchers have already been interested in resolvins such as RvD1 and RvD2 as possible treatments. A practical difficulty is that these molecules can be unstable, making them challenging to manufacture and deliver as medicines.
The UB researchers hope to avoid that problem by delivering DHA instead. They will place DHA inside tiny fatty packages called liposomes and design them to reach neutrophils in the lungs.
Once inside those cells, naturally occurring enzymes may turn the DHA into resolvins. If the method works, the therapeutic molecules would be created directly inside inflamed tissue rather than manufactured elsewhere and transported through the entire body.
The team will test the idea in mouse models of acute lung injury. Their experiments will determine how well the particles reach neutrophils, whether the cells make more resolvins afterward and whether the treatment actually reduces lung injury.
The research is being carried out at the University at Buffalo with funding from the National Heart, Lung, and Blood Institute of the National Institutes of Health. It represents an experimental research program rather than a completed clinical trial or an approved treatment.
The approach has an appealing biological logic: instead of broadly weakening immune activity, it tries to use the body’s own machinery to bring damaging inflammation under control. Targeted delivery might also reduce unwanted effects elsewhere in the body.
Still, several major questions remain unanswered. Nanoparticles that work well in laboratory animals may behave differently in people, and researchers must eventually determine whether the treatment is safe, reaches the correct cells and produces enough resolvins to improve meaningful outcomes.
If those challenges can be overcome, the concept could have uses beyond severe lung injury. Because neutrophils contribute to many inflammatory diseases, the researchers believe similar technology might someday be explored for arthritis, Crohn’s disease and some autoimmune conditions.
For now, the strongest conclusion is that the project offers a creative new direction rather than a ready treatment for ARDS. Its real value will depend on whether the promising biology survives careful animal testing and, eventually, human clinical trials.
For more health information, please see recent studies about how diet influences lung health, and these vegetables could benefit your lung health.
For more information about health, please see recent studies that olive oil may help you live longer, and vitamin D could help lower the risk of autoimmune diseases.
Source: University at Buffalo.
