New research conducted in mouse models suggests that the availability of glucose (a simple sugar) in the lung environment could influence the immune response. The study's authors believe that we may be able to use this information to develop better therapies for respiratory diseases. Millions of people in the United States and across the world live with chronic respiratory conditions. For instance, according to the Office of Disease Prevention and Health Promotion, 25 million people in the U.S. have asthma, a chronic respiratory condition characterized by shortness of breath. With so many individuals having to carefully manage their respiratory health, researchers are constantly on the lookout for discoveries that may bring about new, better therapies. Now, a study conducted in mice — led by researchers from the University of Manchester in the United Kingdom — has found an intriguing link between the presence of glucose in the lung environment and the behavior of macrophages, which are specialized immune cells that can drive inflammation. The study's findings — which feature in the journal Nature Immunology — suggest that, on the one hand, blocking sugar receptors in the lung may help reduce inflammation in chronic respiratory conditions and that, on the other hand, boosting glucose levels in the lung environment could facilitate the immune response in people with certain respiratory infections. This research received funds from numerous supporters, including research bodies, nonprofit organizations, and pharmaceutical companies: the Wellcome Trust in London, the U.K.'s Medical Research Council and Biotechnology and Biological Sciences Research Council, the National Institutes of Health (NIH) in the U.S., Asthma UK, and AstraZeneca. "Respiratory illnesses cause terrible suffering in both the developing and developed world," notes the study's lead researcher, Prof. Andrew MacDonald, Ph.D., from the University of Manchester. "The idea that modifying glucose levels in the lungs could one day be a critical factor in [the] treatment of these conditions is tremendously exciting," he continues. An intriguing find Working with mouse models, the researchers focused on the role that a special type of immune cells — the macrophages — play in respiratory problems and what might influence their response. Macrophages are white blood cells, and their main role is to identify and destroy potentially harmful external bodies, such as bacteria, as well as cellular detritus that could become harmful if it over-accumulates. In the current study, the scientists found an interesting connection between the activity of macrophages in the lungs and the presence of glucose, which is a key cellular nutrient. Prof. MacDonald and the team treated the mice with interleukin-4, a protein that sends signals to immune cells, usually activating their response. Much to their surprise, the researchers found that the macrophages that were unable to take up glucose did not respond to interleukin-4 as they had expected. "During inflammation of the type seen in asthma and parasitic worm infection, it appears that glucose and [the] use of glucose controls macrophage activation in the lungs," notes Prof. MacDonald. "Inflammation is always a delicate balancing act," the researcher told Medical News Today. "Too much can damage us, too little leaves us open to infections, but the ability of cells to take up or use glucose is another area that might be exploitable to fine-tune that balance," he explained. The issue of 'macrophages in mice and men' However, the team has only, as yet, observed the association between glucose uptake in macrophages and inflammatory responses in rodents. In the future, the researchers acknowledge, they will have to confirm whether the same is true in humans. "As this is a fundamental study in mice, clinical applications are really far [off] from now and would require a great deal more research using human cells," Prof. MacDonald told us. He also cautioned that researchers still have quite a limited understanding of how macrophages work in human lungs and that this is a gap that scientists will have to address in the future. "One limitation we have at the moment is in basic understanding of the complexity and diversity of human airway macrophages and how this compares to what we know in mice," Prof. MacDonald said. "Macrophages in mice and men are very similar cell types, but of course, there could be key differences in the way they take up or use glucose, and this will be really important to investigate and understand as much as possible before trying to develop human therapies from this discovery." Prof. Andrew MacDonald, Ph.D. Still, according to the investigators, the current findings suggest that there may be a way to influence glucose levels in the lungs to manipulate macrophage activity as part of treatments for different lung problems. Could sugar inhalation therapy work? "Our data," Prof. MacDonald told MNT, "suggest that future development of therapies targeting glucose could be a way to regulate inflammation in the airways." For instance, he explained to us, "In conditions where inflammation can be damaging, such as asthma, blocking the ability of immune cells to take up glucose could be used to try to reduce damaging inflammation." "On the other hand," he went on to say, "in conditions where there is a need for increased immune cell activation, e.g., to kill an infectious agent, such as the bacteria that cause tuberculosis, administration of glucose could be used to increase beneficial inflammation for a short time." The researchers contend that short-term inhalation therapy could, in the future, become a useful approach in the treatment of respiratory problems. But first, we have to understand exactly how to apply this new knowledge. Source
