Steroid-resistant asthma is known to be related to genetic causes, environmental factors such as tobacco or respiratory viruses, and inflammation, but studies using patient samples or animals are still insufficient. Recently, exposure to particulate matter (PM) has been proposed as one of the causes of steroid resistance. In this study, we investigated changes in cytokines and mTOR activation in patients with steroid-resistant asthma and the role of mTOR in a mouse model of steroid-resistant asthma induced by PM.

In the steroid Non-Responder (NR) group, IL-5, IL-4, IL-13, IL-17, TNF-? with p-mTOR double-positive population of CD4 T cells was significantly higher than that of the Normal or steroid Responder (R) groups.

When PM10 (100 ug) and allergen (Dp) are administered through the intranasal route for 3 weeks, airway hyperresponsiveness, eosinophils, and neutrophils were increased. Histological findings showed severe airway wall muscle cell contraction and increased airway mucus production. In particular, when dexamethasone was administered, neutrophils and lymphocytes decreased, but airway hyperresponsiveness and eosinophil inflammation were insignificant. However, when rapamycin (an mTOR inhibitor) was administered together with PM and Dp, all of the above features showed a significant decrease. Also, in CD62lowCD44+ of CD4 T cells, known as a memory cell marker, IL-5+IL-13+ and IL-13+IL-17+ populations showed a significant decrease compared to the group administered with PM and Dp.

Moreover, as a result of studies in patients and mouse models, the mTOR pathway is thought to play an important role as one of the mechanisms of steroid resistance.