Mechanisms of ketamine-induced immunosuppression

Abstract

Ketamine, a noncompetitive N-methyl-d-aspartate receptor antagonist, is widely used as an intravenous anesthetic agent. It is known to produce increases in blood pressure and stroke volume, which implies its importance in clinical practice. Ketamine has also been shown to possess anti-inflammatory effects. Our previous studies showed that ketamine, at clinically relevant concentrations, can downregulate endotoxin-induced macrophage activation through toll-like receptor-dependent activation of mitogen-activated protein kinases and the transcription factors nuclear factor-kappa B and activator protein-1. As to the responsible mechanisms, considerable attention was devoted to ketamine-involved regulation of proinflammatory gene expression. The assessment of how ketamine regulates proinflammatory gene expressions is significant in determining the signal cascades that are influenced by this anesthetic agent and its clinical application in the tactical use of ketamine in preventing sepsis. Herein, we review the literature on the pharmacodynamics, pharmacokinetics, and possible mechanisms involved in ketamine's immunology.