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, J77 4. Cells were incubated for 18 h under stimulation with lipopolysaccha ride and interferon-gamma or lipoteichoic acid and interferon-gamma, w ith various concentrations of ketamine (6-600 mu mol litre(-1)). Nitri c oxide production was assessed by measuring nitrite, a stable by-prod uct of nitric oxide breakdown, in the medium. Other N-methyl-D-asparta te receptor antagonists, MK-801 (150 mu mol litre(-1)) and dextrometho rphan (150 mu mol 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-activa ted macrophages by up to approximately 65% at the highest ketamine con centration (600 mu mol litre(-1)). Neither MK-801 nor dextromethorphan had an inhibitory effect. Ketamine also suppressed production of tumo ur necrosis factor-alpha. The data show that ketamine inhibited nitric oxide production by activated macrophages probably, in part, via inhi bition of production of tumour necrosis factor-alpha, an autocrine sti mulatory factor for nitric oxide production, but not via the NMDA rece ptor pathway, which is involved in neuronal nitric oxide production.