n-n-dimethylsphingenine and Sepsis

Intestinal epithelial injury in septic patients predicts subsequent development of multiple organ failure, but its regulation by host factors remains unclear. Sphingosine kinase 1 is an enzyme-regulating inflammatory response.. Cecal ligation and puncture was used to induce sepsis in C57BL/6 mice with and without N,N-dimethylsphingosine, a SphK1 inhibitor. Symptom severity was monitored by murine sepsis severity score. The intestinal barrier function was determined using 4KDa fluorescein-dextran. Bacterial load in the bloodstream was determined by 16S rRNA gene amplification.. Our preliminary experimental data showed that expression of sphingosine kinase 1 in ileum was increased by sixfold in septic mice. Pharmacological blockade of sphingosine kinase 1 alleviated septic symptoms. The intestinal permeability and bacterial load in the bloodstream were also reduced in these animals. We hypothesized that inhibition of sphingosine kinase 1 may reduce pro-inflammatory cytokine production, and alleviate intestinal epithelial injury during sepsis. Further mechanistic studies and clinical specimen analyses are warranted.

Topics: Animals; Apoptosis; Bacterial Load; Epithelium; Gastrointestinal Microbiome; Inflammation; Intestines; Mice; Mice, Inbred C57BL; Permeability; Phosphotransferases (Alcohol Group Acceptor); RNA, Ribosomal, 16S; Sepsis; Sphingosine