Researchers at Case Western Reserve University say their discovery of new inflammatory molecules could transform medical treatment.
For many years, scientists believed they had a solid grasp of the biological processes behind asthma, a condition marked by lung inflammation that narrows airways and makes breathing difficult.
They pointed to molecules known as “leukotrienes,” which are released by white blood cells in response to airway irritation or allergens, as the primary cause. These molecules trigger a chain reaction that tightens airways, and several drugs have been designed to block this process.
However, a research team at Case Western Reserve University suggests the real culprits might be different.
“We’ve found molecules that are alike in structure but generated through a completely different chemical pathway in the body,” said lead researcher Robert Salomon, the Charles Frederic Mabery Professor of Research in Chemistry. “We think the molecules we’re calling ‘pseudo leukotrienes,’ may be the dominant players in the inflammatory cascade that causes disease.”
This discovery could shift how scientists approach the treatment of asthma and other inflammatory disorders, potentially extending to neurological diseases such as Parkinson’s and Alzheimer’s. The study, supported by the U.S. National Institutes of Health, has been published online in the Journal of Allergy and Clinical Immunology.
The ‘flames’ of oxidation
The presumed culprits in inflammatory diseases—the leukotrienes—are formed under the control of enzymes that transform lipids, or fatty molecules. By contrast, the pseudo leukotrienes Salomon and his team discovered, are formed by adding oxygen to lipids by molecules called “free radicals.”
“The free radical process is almost like an explosion or a fire,” said Salomon, who is also professor of ophthalmology in the Case Western Reserve School of Medicine. “It’s just like when oxygen reacts with fuel and you get flames. It can easily get out of control.”
People who suffer from asthma may lack enzymes and antioxidant molecules that normally keep a damper on free radicals by scavenging for and destroying them.
The leukotrienes and their mimics initiate inflammation by fitting into a receptor, like a key in an ignition, starting a molecular cascade that constricts the airways of asthmatics. Effective asthma drugs like Singulair block the ignition so the key won’t fit.
“The real importance of this discovery is the possibility of treating these diseases with drugs that prevent the free radical process or moderate it rather than drugs that block the receptor,” Salomon said.
Inflammation: a curse or a benefit?
Not all inflammation is harmful. The body needs inflammation to direct white blood cells to the site of a wound to heal, and it is also involved in memory and development.
Asthma drugs are being repurposed off-label to treat neurological diseases. But these treatments could also block the beneficial effects of the leukotrienes.
“If the molecules that are causing the problem are not the leukotrienes but these other molecules,” Salomon said, “a better treatment would be to just stop the formation of these other molecules rather than gumming up the ignition.”
The study
Salomon and his colleagues used their decades of experience studying the oxidation of lipids—and some chemical intuition—to guess that pseudo leukotrienes existed. They made the molecules in the laboratory to develop methods to detect them.
They obtained urine samples from patients diagnosed with mild or severe asthma and compared them to urine from people who don’t suffer from the disease.
Not only were pseudo leukotrienes found in the asthma patients’ urine, but also the amounts correlated directly to the severity of the disease. Severe asthma sufferers or even those suffering mild asthma had four to five times more than the controls. The researchers suggest this could be a new biomarker to test for the severity of disease and monitor the effectiveness of therapies.
The researchers’ next plan is to investigate whether these pseudo leukotrienes are involved in other respiratory diseases, like respiratory syncytial virus (commonly known as RSV) and bronchiolitis in babies, and chronic obstructive pulmonary disease.
Reference: “Radical-induced Lipid Oxidation Produces a Torrent of Leukotriene-like Agonists in Severe Asthma” by Si-Yang Liu, Mikhail Linetsky, Abby Hite, Yu-Shiuan Cheng, Masaru Miyagi, Serena C. Zhu, Hong Zeng, Siqi Huang, Myra Qin, Emma Sintic, Carolyn M. Koutures, Abigail Meneses, Olivia R. Laniak, Sailaja Paruchuri, Lakshminarayan R. Teegala, Kaixi Cui, Fariba Rezaee and Robert G. Salomon, 15 October 2025, Journal of Allergy and Clinical Immunology.
DOI: 10.1016/j.jaci.2025.09.027
Funding: National Institutes of Health, National Eye Institute
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