Lactic acid attenuates LPS-induced cytokine production in mast cells (INC6P.320)

Abstract Elevated lactate levels and attenuated lactate clearance following hospital admission have been associated with increased mortality in sepsis patients. While some effects of lactate on LPS stimulation have been examined in monocytes and macrophages, mast cells have not been examined. Therefore, the purpose of this study was to examine the effect of lactic acid on LPS-induced mast cell activation. Methods: Murine bone marrow derived mast cells were cultured in medium with or without lactic acid for 24 hours. Additionally, sodium lactate and formic acid were examined. Following the pre-incubation period, LPS was added and supernatants were collected after 16 hours for cytokine ELISA analysis. Results:Pre-incubation with lactic acid significantly reduced cytokine (TNF, IL-6) and chemokine (MCP-1, MIP-1a) secretion following LPS stimulation. Sodium lactate pre-incubation did not change cytokine production. However formic acid, which has a similar pKa to lactic acid, also reduced cytokine production compared to the control. Discussion:Lactic acid attenuates LPS-induced mast cell activation, an effect that appears to be dependent upon pH rather than acid chemical structure. Our results suggest that lactic acid may play a suppressive role in mast cell activation during sepsis.