Ketamine modulates the stimulated adhesion molecule expression on human neutrophils in vitro

Cytokine production, neutrophil adhesion to endothelial cells, and release of reactive oxygen species are thought to be critical events in sepsis or i schemia/reperfusion. Modulation of leukocyte responses by anesthetics may h ave an important role in limiting tissue injury under these conditions. The refore, we investigated the effect of ketamine on the expression of CD18, C D62L, and oxygen radical production of human neutrophils in vitro and on in terleukin-6 production in endotoxin-stimulated human whole blood. Ketamine inhibited both the N-formyl-methionyl-leucyl-phenylalanine- and phorbol 12- myristate 13-acetate-induced up-regulation of CD18 and shedding of CD62L, d etermined by now cytometry, in a concentration-dependent manner. Ketamine a lso caused a significant suppression of oxygen radical generation of isolat ed human neutrophils. In addition, there was a significant decrease in endo toxin-stimulated interleukin-6 production in human whole blood. The inhibit ory effects were similar for racemic ketamine and its isomers S(+)-ketamine and R(-)-ketamine, suggesting that the inhibition of stimulated neutrophil function is most likely not mediated through specific receptor interaction s. Implications: Modulation of leukocyte responses by anesthetics may have an important role in limiting tissue injury in sepsis or ischemia/reperfusi on. Therefore, we examined the effect of ketamine on stimulated neutrophil functions in vitro. These neutrophil functions were significantly inhibited by ketamine, independent of whether the racemic mixture or isomers were te sted.