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 ischemia/reperfusion. Modulation of leukocyte responses by anesthetics may have an important role in limiting tissue injury under these conditions. Therefore, we investigated the effect of ketamine on the expression of CD18, CD62L, and oxygen radical production of human neutrophils in vitro and on interleukin-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, determined by flow cytometry, in a concentration-dependent manner. Ketamine also caused a significant suppression of oxygen radical generation of isolated human neutrophils. In addition, there was a significant decrease in endotoxin-stimulated interleukin-6 production in human whole blood. The inhibitory 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 interactions.


CONCLUSIONS
Modulation of leukocyte responses by anesthetics may have an important role in limiting tissue injury in sepsis or ischemia/reperfusion. 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 tested.
Weigand
M A
MA
Department of Anesthesiology, University of Heidelberg, Germany.
Schmidt
H
H
Zhao
Q
Q
Plaschke
K
K
Martin
E
E
Bardenheuer
H J
HJ
D000778:Anesthetics, Dissociative / Q000737:chemistry / Q000494:pharmacology*; D018821:CD18 Antigens / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D015850:Interleukin-6 / Q000096:biosynthesis; D007649:Ketamine / Q000737:chemistry / Q000494:pharmacology*; D019041:L-Selectin / Q000096:biosynthesis; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013237:Stereoisomerism; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000778:Anesthetics, Dissociative; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D018691:Excitatory Amino Acid Antagonists; D007202:Indicators and Reagents; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D013481:Superoxides; D019041:L-Selectin; D007649:Ketamine