Lung inflammation may make traumatic events harder to forget

Recent research highlights a troubling connection between severe airway inflammation and the cognitive processing of traumatic experiences in mice. Findings indicate that such inflammation can significantly impair the ability of these animals to learn when a perceived danger has subsided, suggesting a direct link between lung health and emotional regulation.

“Many individuals experience trauma, yet only approximately 5 to 10 percent of those affected develop post-traumatic stress disorder (PTSD),” remarks Renu Sah from the University of Cincinnati in Ohio. Previous investigations have indicated that inflammation, particularly in lung conditions like asthma, may exert influence over the development of PTSD. For example, military veterans diagnosed with PTSD show an eightfold increase in asthma prevalence.

To explore this relationship further, Sah and her research team examined eight mice exhibiting severe asthma-like symptoms. The scientists triggered allergic reactions and inflammation in the mice’s lungs using house dust mites, following which the animals were placed in a cage and subjected to mild electric shocks.

Over the subsequent six days, the researchers returned the mice to the cage daily for five-minute intervals, measuring the duration of time they froze in a fear-induced state. The results were telling; the afflicted mice froze for approximately 40 percent of the final session—twice the amount of time spent frozen by a control group of 11 healthy mice that experienced the same shocks without lung inflammation.

Notably, both groups displayed similar fears on the day following the shocks, highlighting an immediate response to danger. However, the inflammatory group’s extending fear response indicated a dysfunction in their brain’s ability to assess when the danger had passed. “In PTSD patients, this recognition process is impaired, resulting in prolonged fear memories,” Sah explains.

The researchers replicated this experiment using a different group of mice suffering from lung inflammation but administered a drug that inhibits the inflammatory molecule interleukin-17A. The results showed that these treated mice froze for significantly less time compared to untreated mice, indicating a successful modulation of the fear response.

Additional analysis revealed that immune cells in a specific brain region called the subfornical organ possess receptors for interleukin-17A. Unlike most brain areas protected by a blood-brain barrier, the subfornical organ provides a unique channel where the brain can detect and respond to bodily inflammatory responses. This connection enables the brain to regulate emotional responses in coordination with physical conditions.

By employing chemogenetics to inhibit this pathway in the severely inflamed mice, researchers observed reduced fear responses in situations involving previous trauma. “Essentially, severe inflammatory responses in the lungs can disrupt cognitive functions and a person’s ability to process traumatic events,” remarks Sah. Given parallels in the fear circuitry between humans and mice, these findings may have direct implications for human health as well.

Furthermore, related studies have demonstrated that chronic psychological stress can suppress immune responses, leading Sah to theorize that heightened immune reactions from lung inflammation may diminish psychological functioning instead. “The body might redirect its resources to deal with respiratory threats at the expense of cognitive processing,” she proposes.

According to Douglas Vanderbilt from Children’s Hospital Los Angeles, these insights are pivotal for understanding the intricate connections linking our mental and physical health. They might illuminate why children with severe asthma demonstrate heightened PTSD symptoms. However, Vanderbilt cautions that the mechanisms at play are likely complex and multifaceted, and stress from asthma attacks could also contribute to PTSD risk.

As the study exclusively focused on male mice, Sah notes that variations between genders warrant further investigation. Understanding these distinctions may ultimately enhance our ability to identify individuals at greater risk for PTSD, such as children struggling with severe asthma. This could lead to novel therapeutic avenues aimed at alleviating inflammation as a means of treating PTSD.