Importantly, we also found that the secretion of pleiotropic cytokines such as IL-6 and IL-33, which are predominantly observed in lung tissue and lead to airway inflammation [22], was significantly reduced in the BALF of SphK2−/− mice compared with the levels in the BALF of WT mice (Figure 3F and 3G), strongly suggesting a critical role of SphK2 in inducing pulmonary inflammation after chronic CS exposure. This evidence concerns the gene SPHK2 and inflammatory response.