Ketamine inhibits nitric oxide production in mouse-activated macrophage-like cells

Br J Anaesth. 1996 Aug;77(2):238-42. doi: 10.1093/bja/77.2.238.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Dissociative / pharmacology*
  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Interferon-gamma / immunology
  • Ketamine / pharmacology*
  • Lipopolysaccharides / immunology
  • Macrophage Activation / physiology
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide / biosynthesis*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Teichoic Acids / immunology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Anesthetics, Dissociative
  • Lipopolysaccharides
  • Receptors, N-Methyl-D-Aspartate
  • Teichoic Acids
  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • lipoteichoic acid
  • Ketamine
  • Interferon-gamma