Kepler et al. (Kepler et al., 2013b) showed that exposing human NP and AF cells to IL-1β or TNF-α can upregulate the expression of substance P. The contents of other inflammatory factors such as IL-6 and IL-8 were further significantly increased by substance P. In addition, the expression of some other inflammatory molecules was also upregulated by exposure to IL-1β, such as nitric oxide (NO), cyclooxygenase (COX)-2 and prostaglandin E (PGE)-2 (Wang et al., 2019b; Jin et al., 2019). This evidence concerns the gene TNF and atrial fibrillation.