Inhibitory effects of Leishmanial sphingolipid on Endotoxin induced macrophage activation and sepsis associated inflammatory injury

Abstract

Sepsis is the reflection of systemic immune response that manifests in the sequential inflammatory process in presence of infection with excessive production of inflammatory mediators and causes severe tissue injuries. Total lipid of attenuated Leishmania donovani establish as a bioactive. Moreover, sphingolipids moderate various cellular processes. So, this finding encourages us to evaluate inflammatory response in system using the microbial sphingolipid.In this study, we have used bacterial endotoxin stimulated macrophages to evaluate the efficacy of leishmanial sphingolipid (LSPL) towards the amelioration of inflammatory mediators (TNF‐α, IL‐1β, IL‐6, IL‐17, IL‐10) and transcriptional factors with associated TLR4‐CD14 expression. In vivo system, endotoxin induced murine sepsis model was used in focusing on multiple organ injury (Lungs, Liver, and Kidney) and status of different cytokine‐chemokine(s) storm. Due to the effect of LSPL, endotoxin induced inflammatory cytokine‐chemokine(s) levels were significantly reduced in serum and other major organs with the reduction of vascular permeability factors and suppressed the expression of cell adhesion molecule in septic mice evident by immunochemical approaches.These findings indicate that LSPL may prove to be a potential anti‐inflammatory agent as protection against bacterial sepsis with associated organ injury.