Environmental Exposures: Evolving Evidence for Their Roles in Adult Allergic Disorders

Kaoru Harada; Rachel L. Miller

Disclosures

Curr Opin Allergy Clin Immunol. 2022;22(1):24-28. 

In This Article

Mechanisms and Biomarkers

Much of the recent mechanistic work addressing which inflammatory pathways are elevated following environmental exposures have focused on determining relevant biomarkers, such as determinants of altered epigenetic regulation. For example, Li and colleagues conducted a randomized, double-blind crossover study to investigate changes in DNA methylation following diesel and allergen exposure among 11 allergen-sensitized adults. Endobronchial biopsies, bronchoalveolar lavages (BAL), and spirometry were obtained 48 h following exposure to filtered air, allergen, and allergen and diesel. Levels of DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) methylcytosine dioxygenases, that mediate hydroxymethylation, were analyzed from endobronchial biopsies. Among all participants, there was a positive correlation between DNMT and TET levels and lung function. Participants were then categorized by baseline levels of biomarkers of DNA methylation. Those with high TET2 had higher baseline levels of IL-8 in BAL, and allergen exposure was associated with decreased IL-8, implying that TET2 downregulates IL-8.[21]

Another novel experiment evaluated the role of ceramide, a key metabolite in the sphingolipid pathway, in allergen-induced airway inflammation and apoptosis. Mice were sensitized with either dust mite or the fungal allergen Alternaria alternata over 2 weeks and then underwent allergen challenge. Analysis of lung tissue demonstrated apoptosis of airway epithelial cells, increased reactive oxygen species and ceramide levels, and activation of the apoptosis precursor caspase 3. Intraperitoneal treatment with myriocin prior to allergen challenge reduced ceramide levels, allergen-induced apoptosis, oxidative stress, and neutrophilia. In comparison, dietary supplementation with antioxidative α-tocopherol reduced reactive oxygen species but not ceramide levels nor apoptosis, suggesting that oxidative stress is not the cause of allergen-induced ceramide generation or apoptosis. To examine whether ceramide may be used as a biomarker in asthmatic patients, the investigators then measured ceramide levels from BAL fluids in 10 severe asthmatics, 5 nonsevere asthmatics, and 5 healthy controls. Ceramide levels were higher in adults with severe asthma, but not mild asthma, compared to healthy controls. Among all of the participants, ceramide levels correlated with airway obstruction on spirometry and neutrophil infiltration in BAL.[22] Combined, these results suggested that allergic airway inflammation may be characterized by ceramide generation and apoptosis.

processing....