Ketamine inhibits nitric oxide production in mouse-activated macrophage-like cells.
We have investigated the effects of ketamine on nitric oxide produced by activated macrophages using a murine macrophage-like cell line, J774. Cells were incubated for 18 h under stimulation with lipopolysaccharide and interferon-gamma or lipoteichoic acid and interferon-gamma, with various concentrations of ketamine (6-600 mumol litre-1). Nitric oxide production was assessed by measuring nitrite, a stable by-product of nitric oxide breakdown, in the medium. Other N-methyl-D-aspartate receptor antagonists, MK-801 (150 mumol litre-1) and dextromethorphan (150 mumol litre-1) were also tested. In addition, we studied the effects of ketamine on production of tumour necrosis factor-alpha by activated macrophages. Ketamine inhibited nitrite production dose-dependently with both lipopolysaccharide- and lipoteichoic acid-activated macrophages by up to approximately 65% at the highest ketamine concentration (600 mumol litre-1). Neither MK-801 nor dextromethorphan had an inhibitory effect. Ketamine also suppressed production of tumour necrosis factor-alpha. The data show that ketamine inhibited nitric oxide production by activated macrophages probably, in part, via inhibition of production of tumour necrosis factor-alpha, an autocrine stimulatory factor for nitric oxide production, but not via the NMDA receptor pathway, which is involved in neuronal nitric oxide production.
Shimaoka
M
M
Department of Anaesthesiology, Osaka University Hospital, Japan.
Iida
T
T
Ohara
A
A
Taenaka
N
N
Mashimo
T
T
Honda
T
T
Yoshiya
I
I
D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D007649:Ketamine / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation / Q000502:physiology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013682:Teichoic Acids / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000778:Anesthetics, Dissociative; D008070:Lipopolysaccharides; D016194:Receptors, N-Methyl-D-Aspartate; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C009900:lipoteichoic acid; D007649:Ketamine; D007371:Interferon-gamma