Ketamine does not inhibit inflammatory responses of cultured human endothelial cells but reduces chemotactic activation of neutrophils
Autor: | S, Zahler, B, Heindl, B F, Becker |
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Rok vydání: | 1999 |
Předmět: |
Inflammation
Anesthetics Dissociative Umbilical Veins Interleukin-6 Neutrophils Tumor Necrosis Factor-alpha Chemotaxis Interleukin-8 Macrophage-1 Antigen Intercellular Adhesion Molecule-1 Chemotaxis Leukocyte Cytokines Humans Ketamine Endothelium Vascular E-Selectin Cell Adhesion Molecules Cells Cultured |
Zdroj: | Acta anaesthesiologica Scandinavica. 43(10) |
ISSN: | 0001-5172 |
Popis: | Ketamine is a widely used general anaesthetic, which has been reported to inhibit neutrophil function and neutrophil-endothelial interaction. To date, however, it is unknown whether ketamine has any direct effects on endothelial cells with respect to inflammation. Therefore, we investigated the influence of varying concentrations of ketamine (0.5, 1, and 3 microM) on the endothelial expression of cytokines and adhesion molecules with relevance for inflammation.Cultured human umbilical vein endothelial cells were stimulated with tumor necrosis factor alpha (TNFalpha, 2.5 ng/ml) for 4 h in the absence or presence of ketamine. The adhesion molecules ICAM-1 and E-selectin on the endothelial cells were measured by flow cytometry. Release of the proinflammatory cytokines IL-6 and IL-8 by endothelial cells was quantified by ELISA. The acute effect of ketamine on leukocyte activation by the supernatant of endothelial cells pre-stimulated with TNFalpha (4 h) was tested by flow cytometric measurement of CD11b, a leukocyte activation marker, after 15 min of coincubation.TNFalpha caused dramatic upregulation of both adhesion molecules (15-fold and 5-fold vs. control for ELAM-1 and ICAM-1, respectively) and of both cytokines (500-fold and 1.8-fold for IL-6 and IL-8, respectively). No concentration of ketamine employed in our study had any effect on these inflammatory parameters. However, activation of leukocytes by supernatant of TNFalpha-conditioned endothelial cells (70% increase of CD11b) was attenuated by coincubation of the PMN with 0.5 and 5 microM ketamine (47% and 44% increase, respectively).These data suggest that ketamine exerts its antiinflammatory actions primarily via inhibition of leukocyte reactivity. Indeed, no inhibition of endothelial responses was detectable in our study. |
Databáze: | OpenAIRE |
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