ScienceDaily — An immune-system protein already used to treat diseases like multiple sclerosis, hepatitis C and a variety of cancers might also aid asthma patients, UT Southwestern Medical Center researchers have found.
The investigators determined that the protein interferon blocks the development of a population of immune cells known to cause asthma. These cells are members of a class of T lymphocytes, called T helper 2 cells, or Th2 cells. Under normal circumstances, Th2 cells help protect against infections by secreting chemicals that induce inflammation; however, in some individuals, these Th2 cells can also promote allergic responses to normally harmless substances, including animal dander, pollens and pollutants. Once Th2 cells become reactive to these substances, they promote all of the inflammatory processes common to allergic diseases like asthma and atopic dermatitis.
The findings, available online and in the July 15 issue of the Journal of Immunology, suggest that interferon might be a valuable and readily available therapy for individuals with asthma.
"This finding is incredibly important, because humans are being treated with interferon for a variety of diseases, yet no one has tried treating asthma patients with interferon," said Dr. J. David Farrar, assistant professor of immunology and molecular biology at UT Southwestern and senior author of the study. "The current therapies for asthma are inhalers and steroids, both of which offer only temporary relief."
Asthma results in approximately 200,000 pediatric hospitalizations each year, more than for any other childhood disease. About 20 million people have been diagnosed with asthma in the U.S.
In the current study, the researchers showed in isolated human cells that interferon blocks the development of nascent Th2 cells and inhibits cells that already have become Th2 cells by interfering with a regulatory protein called GATA3, a transcription factor Th2 cells express to regulate their function.
"Interferon is blocking the development of these cells and their stability, and it's doing this by targeting the very transcription factor that regulates their development and stability in the first place," Dr. Farrar said. "By targeting this transcription factor, we've turned off the key component that regulates the entire process."
The findings, he said, provide proof-of-principle that targeting this particular group of cells with interferon might be an effective therapy for those with asthma.
"The study has confirmed that it's the Th2 cells that you really want to target," he said. "If you can stop a Th2 cell from ever developing, and if you can take a Th2 cell that has already become one and stop it from secreting these asthma-causing chemicals, then that's really the 'Holy Grail' of treating asthma."
The next step, Dr. Farrar said, is to study whether interferon will prevent Th2 cells taken straight from asthma patients from secreting the chemicals known to induce asthma.
"If interferon works against these cells, I think that would be an excellent basis for beginning a clinical trial and treating asthma patients," Dr. Farrar said. "We've been treating humans with interferon for a long time, so we don't have to go through early-phase safety trials. We already have information about its toxicity."
王中王鉄算盘开奖结果，Other UT Southwestern researchers involved in the study were Jonathan Huber, lead author and student research assistant in immunology; Hilario Ramos, former student research assistant in immunology; and Dr. Michelle Gill, assistant professor of pediatrics and internal medicine.
The study was funded by the National Institutes of Health and Exxon Mobil Corp.
ScienceDaily — For many people afflicted by asthma, treatment can be a frustrating and time-consuming experience. After their initial diagnosis, asthmatics find themselves caught in a trial and error process that can last for months, as doctors gradually escalate their medications to treat their condition effectively with minimal side effects. And until the right medicine and dosage are found, patients continue to suffer attacks that strike without warning and can leave them struggling for breath for hours or even days.
The problem is that asthma isn't a single disease. Instead, it's a set of related symptoms that spring from a variety of underlying processes, both environmental and genetic. These different processes influence the rate of progression, lung function decline and response to therapy. Today, researchers believe that asthma treatment will be improved by matching the right therapy to the right asthma subtype -- but trial and error still play a large role in making the right match.
Researchers in the University of Texas Medical Branch at Galveston's Institute for Translational Sciences think modern medicine can do better than that. In a paper now online in the "Early View" section of the journal Clinical and Translational Science, members of the ITS Phenotypes of Severe Asthma Multidisciplinary Translational Team describe their progress developing new techniques that will allow clinicians to quickly identify particular asthma subtypes that may ultimately show them how to prescribe the proper medication to prevent or mitigate future attacks.
"In an earlier study, we found that patterns of proteins in the airway lining fluid are connected to particular asthma subgroups," said Dr. Allan Brasier, lead author of the paper and director of the ITS. "For this project, our MTT worked with the national Severe Asthma Research Program, using a much larger sample of people with asthma. We were looking for the best way to relate protein patterns to specific disease subtypes."
To begin, Brasier and other members of the team examined data from 1,048 participants in the SARP -- a National Heart, Lung and Blood Institute-created network of 10 different asthma research centers -- and arranged the patients into four largely separate categories. Two of the categories contained patients in whom one or another specific type of immune cell caused the inflammation that constricted their airways; one was composed of patients whose bronchial tubes opened readily when they were treated with an albuterol inhaler; and one contained the patients who responded most strongly to exposure to methacholine, a drug commonly used to test for asthma.
The researchers analyzed saline solution washings of airway lining fluid from the lungs of 76 anesthetized SARP volunteers and applied many simultaneous measurement techniques to measure levels of 20 key cytokines . This information was analyzed and used for computer modeling to scan for patterns in the protein measurements and match each patient with one of the four subtypes.
"We applied four different computational methods to predict what specific asthma subset each patient belonged to based on cytokine patterns and two worked very well, giving us 80 to 90 percent accuracy," Brasier said. "We hope to improve that to 100 percent, of course, but we still see this as a landmark study -- because for the first time we're starting to tie protein profiles to specific asthma subsets, which leads directly to getting people the right treatment for asthma much more rapidly."
"One of the goals of the ITS-supported MTTs is to partner with national consortia or networks to increase the impact of their studies; this linkage with the SARP program is a good example of this approach," Brasier continued. The partnership was facilitated by team member Dr. William Calhoun, who has worked closely with SARP for many years. In addition to Brasier and Calhoun, authors of the paper include biostatisticians Sundar Victor and Hyunsu Ju; Drs. William Busse and Nizar Jarjour of the University of Wisconsin-Madison; Douglas Curran-Elliott of National Jewish Health in Denver; Eugene Bleecker of Wake Forest University School of Medicine, Winston-Salem; Dr. Mario Castro of Washington University in St. Louis; Dr. Kian Fan Chung, Imperial College, London; Dr. Benjamin Gaston of the University of Virginia, Charlottesville; Dr. Elliot Israel of Brigham and Women's Hospital, Boston; Dr. Sally Wenzel of the University of Pittsburgh; and Dr. Serpil Erzurum of the Cleveland Clinic, Cleveland.
The UTMB Clinical and Translational Science Award, the National Institutes of Health, the National Heart, Lung and Blood Institute and the Severe Asthma Research Program supported this research.
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The above story is reprinted from materials provided by University of Texas Medical Branch at Galveston.