Why do some people with asthma experience severe flare-ups after viral infections, while others show hardly any symptoms? A research team led by DZL scientists at the Research Center Borstel, Leibniz Lung Center (FZB), in collaboration with DZL colleagues from the sites BREATH (Hannover) and CPC-M (Munich), has now uncovered an underlying mechanism and identified a biomarker that may predict severe exacerbations and open new therapeutic avenues. The findings were published in the journal Allergy.
Respiratory viral infections pose a significant risk for people with asthma: while some can regain control of their symptoms through medication adjustment, others suffer life-threatening exacerbations that may require hospitalization. Until now, it has not been possible to predict which patients are particularly at risk, nor are there targeted therapies for such acute episodes.
DZL researchers from the fields of epigenetics of chronic lung diseases and lung immunology have now identified a key mechanism: in a mouse model, the cytokine interleukin-6 (IL-6) was shown to be released particularly early and in large quantities in response to the trigger of an exacerbation. The higher the IL-6 levels, the more severe the disease became. However, when IL-6 was blocked—either through antibodies or genetic modification—the animals were protected from exacerbation.
The scientists also demonstrated that airway epithelial cells produce increasing amounts of IL-6 after repeated viral infections. This heightened responsiveness is epigenetically imprinted: a specific methylation pattern of the IL6 gene acts as a form of “cellular memory.” This work is the first to extend the concept of “trained immunity” to structural epithelial cells lining the airways.
Importantly, this methylation pattern was also identified in samples from people with asthma. It correlates with elevated IL-6 expression and increased use of rescue medication—and can even predict future exacerbations. These findings could enable clinicians to identify patients at high risk and pave the way for anti-IL-6–based therapies in asthma.
