Ephedrine hydrochloride inhibits PGN-induced inflammatory responses by promoting IL-10 production and decreasing proinflammatory cytokine secretion via PI3K/Akt/GSK3β pathway (P5048)

Abstract

Abstract The approaches to control the inflammatory responses and reduce the mortality rate of sepsis are still not very effective in clinics and new potential drugs are needed to be confirmed to be useful in the induction of anti-inflammatory response. Ephedrine hydrochloride (EH) is a compound widely used for cardiovascular diseases, especially to treat hypotension caused by anesthesia or overdose of antihypertensive drugs. In this study, we reported that EH also plays an important role in the control of inflammatory response. It increases interleukin 10 (IL-10) and decreases proinflammatory cytokine (IL-6, TNF-α, IL-12, and IL-1β) expression in response to gram-positive cell wall component peptidoglycan (PGN) in primary peritoneal macrophages and Raw264.7 cells. The anti-inflammatory role of EH was also observed in experimental peritonitis mouse model induced by intraperitoneally PGN injection. Phosphatidylinositol 3-kinase (PI3K)/Akt pathway was found to be responsible for EH-enhanced IL-10 production and EH-decreased IL-6 expression. Therefore, our results illustrated that EH can help to maintain immune equilibrium and diminish host damage by balancing the production of proinflammatory cytokines and anti-inflammatory cytokine after PGN challenge. EH may be a new potential anti-inflammatory drug in treatment of severe invasive gram-positive bacterial infection.