Immunomodulatory activity of ketamine in human astroglial A172 cells: Possible relevance to its rapid antidepressant activity

• The immunomodulatory effects of ketamine were studied in human astroglial cells.
• The effects of ketamine were investigated in cells simulated by a mix of cytokines.
• The effects of ketamine were investigated in unstimulated cells.
• Ketamine suppressed IL-6 and TNFα production and gene expression.
• Ketamine augmented IL-1β and IL-8 production and gene expression.

To determine if the immunomodulatory effect of ketamine is relevant to its rapid antidepressant activity, cultured human astroglial cells were incubated with ketamine, cytokine mix, or both. At 24 h, ketamine dose-dependently (100–500 μM) decreased IL-6 and TNFα production and gene expression and, at clinically relevant concentration (100 μM), augmented IL-β release and gene expression in both unstimulated and cytokine-stimulated cells. In unstimulated cells, ketamine also increased IL-8 production and mRNA expression. The reduction in IL-6 mRNA was significant within 1 h in unstimulated cells and at 4 h after stimulation. Ketamine suppressed the production of the only established depression-relevant proinflammatory cytokines, IL-6 and TNFα.