Effects of ceramide pathway inhibition on the inflammatory response in lipopolysacharide-triggered lung injury

Background: Ceramide participate in various pathophysiologic events in ARDS and can be formed through several pathways. Otherwise, the profile of inflammatory response triggered by each pathway is not yet elucidated. Objectives: To assess the inflammatory response in both de novo [serine palmitoyl transferase (SPT) and dihydroceramide synthase (DS)] and sphingomyelinase [acid (ASM) and neutral sphingomyelinase (NSM)] pathways in a LPS-induced injury model. Methods: It was used 4 ceramide metabolism inhibitors [desipramine (ASM inhibitor) (3, 10 and 30 mg/kg, n=5/dose)], [GW4869 (NSM inhibitor) and myriocin (SPT inhibitor) (both at 0,3; 1 and 3 mg/kg, n=5/dose/inhibitor) and fumonisin (DS inhibitor) (1, 3 and 10 mg/kg, n=5 /dose)], administered intraperitoneally 1 h before LPS intratracheal instillation. So, to each inhibitor (n=30), more 3 groups (n=5/group) were added: Control groups (saline 50 uL, i.t.), mice receiving the inhibitor maximum dose used to each inhibitor and LPS group (2 mg/kg). The levels of IL-1β, IL-6, TNF-α and KC were evaluated on lung tissue by ELISA. Results: Desipramine (3 mg/kg) was able to decrease the TNF-α levels compared to the LPS group (162.3±63,0 vs . 370.4±129.4 pg/mg ptn; p=0.001). GW4869 (3 mg/kg) decreased the release of IL-1β (3 mg/kg) compared to LPS (114.2±22.3 vs . 243.1±42.4 pg/mg ptn; p vs. 315.8±31.6 pg/mg ptn, p=0.003 and 133,9±22,9 vs . 253,9±39,9 pg/mg ptn, p Conclusions: The inhibition of each enzyme involved therein yields different outcomes on the LPS-induced lung inflammation.