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Ketamine inhibits nitric oxide production in mouse-activated macrophage-like cells
1Department of Anaesthesiology, Osaka University Hospital, Japan.
Abstract:
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.
Insights
Ketamine significantly reduces nitric oxide (NO) production in activated macrophages, likely by suppressing tumor necrosis factor-alpha. This effect does not involve the NMDA receptor pathway, suggesting a distinct mechanism for immune cell modulation.
Area of Science:
- Immunology
- Pharmacology
Background:
- Macrophages play a crucial role in immune responses, producing nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α).
- Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has potential immunomodulatory effects that require investigation.
Purpose of the Study:
- To investigate the effects of ketamine on nitric oxide production by activated macrophages.
- To determine if ketamine's effects on NO production are mediated through the NMDA receptor pathway.
- To examine ketamine's impact on TNF-α production in macrophages.
Main Methods:
- Murine macrophage-like cell line (J774) stimulated with lipopolysaccharide (LPS) or lipoteichoic acid (LTA) and interferon-gamma (IFN-γ).
- Treatment with various concentrations of ketamine, MK-801, and dextromethorphan.
- Measurement of nitrite (NO breakdown product) and TNF-α levels in culture supernatants.
Main Results:
- Ketamine demonstrated a dose-dependent inhibition of nitrite production in both LPS- and LTA-activated macrophages, reducing it by up to 65% at 600 μmol/L.
- Neither MK-801 nor dextromethorphan inhibited nitrite production.
- Ketamine also suppressed the production of TNF-α.
Conclusions:
- Ketamine inhibits nitric oxide production in activated macrophages, potentially through the suppression of TNF-α.
- The inhibitory effect of ketamine on macrophage NO production is not mediated via the NMDA receptor pathway.