In CF mice, melatonin treatment helps normalize infection response
Hormone know for promoting sleep may have benefits for CF patients: Study
Treatment with melatonin, a hormone best known for its sleep-promoting role, was found to normalize inflammatory responses to airway infection and reduce the burden of infection-causing bacteria in a mouse model of cystic fibrosis (CF), per new research by U.S. scientists.
“Long-term systemic treatment with melatonin is an effective therapy in a CF mouse model that normalizes the response to airway infection,” the researchers wrote.
The team noted that, despite “highly effective” treatments that have been developed for CF in recent years, “there is still a need for supplemental therapies that further augment the control of inflammation.” Thus, “approaches to mitigate the severity of infections and of immune responses are still needed for the treatment of cystic fibrosis,” they wrote.
According to the scientists, their new findings “suggest that melatonin may have benefits as an anti-inflammatory therapy for [people with CF].”
The study, “Efficacy of melatonin treatment in a cystic fibrosis mouse model of airway infection,” was published in the journal Scientific Reports.
Researchers cite need for more treatments for airway inflammation
CF is characterized by the buildup of thick and sticky mucus throughout the body, which drives a wide range of symptoms. In the lungs, this mucus offers a prime breeding ground for bacteria and other microbes, leading to airway infections that cause inflammation and lung damage.
Highly effective CFTR modulator therapies that have become available in recent years have substantially changed the outlook for CF and have eased patient symptoms. However, certain aspects of CF, including airway inflammation, may not be completely reversed by these treatments. Moreover, not all patients are eligible to receive them.
“Supplemental treatments to further target inflammatory and immune pathways are still needed to effectively treat CF patients,” the researchers wrote.
Melatonin is a naturally occurring hormone that’s best recognized for its role in regulating sleep-wake cycles. Melatonin supplements are commonly used to promote sleep.
The hormone also has potent anti-inflammatory effects and has demonstrated an ability to ease inflammation in airway diseases. It could thus possibly have anti-inflammatory benefits in CF, according to this team of researchers, from Case Western Reserve University in Ohio.
In a mouse model of CF, melatonin production was found to be diminished relative to healthy mice. Moreover, in a previous study involving CF patients, daily melatonin treatment was associated with improvements in sleep, as well as reductions in exhaled nitrite, a molecule that’s associated with inflammation.
Melatonin treatment seen to potentially improve overall health of mice
Now, the researchers used a mouse model of the disease to further explore whether melatonin treatment could ease CF-related airway inflammation. The mice were treated with melatonin in their drinking water, or received regular drinking water, for a little over two months. The airways of the animals were then infected with Pseudomonas aeruginosa, a common infection-causing bacteria in CF.
The so-called CF mice generally had a more exacerbated response to the lung infection than healthy, or wild-type mice, exhibiting a higher burden of bacteria in the lungs and signs of a more exaggerated inflammatory response.
Melatonin treatment in the CF model helped to normalize those responses. Relative to CF mice not given melatonin, the animals who received the supplement had a lower amount of bacteria in the lungs and an inflammatory immune cell profile that looked more similar to wild-type mice.
Levels of inflammatory signaling molecules in lung tissue also were reduced with melatonin treatment in the CF model. The melatonin-treated CF mice lost significantly less weight after the infection than mice given regular drinking water, suggesting it improved their health and overall resilience to infection, according to the team.
Melatonin may represent a safe and easily accessible approach to augment therapy with [high-efficacy CFTR modulators] to help control infection and immune response.
Short-term melatonin treatment, in which the therapy was given for one week prior to the P. aeruginosa infection, still reduced the amount of bacteria present in the lungs. However, it didn’t influence inflammation.
An approach wherein melatonin was administered directly to the lungs, via a thin flexible tube called a bronchoscope, did not show beneficial effects in terms of bacteria levels, weight, or inflammation.
The scientists had initially expected that direct treatment of the airways would be the more effective method for easing infection-related inflammation. But they noted several factors that could explain why this wasn’t the case, including insufficient dosing or treatment time.
The systemic long-term melatonin treatment, conversely, showed promise for controlling airway infections and inflammation in CF.
“Melatonin may represent a safe and easily accessible approach to augment therapy with [high-efficacy CFTR modulators] to help control infection and immune response,” the researchers wrote.
More studies will be needed, according to the team, to assess the effects of melatonin treatment in airway infections caused by pathogens other than P. aeruginosa.
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