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ANESTHETIC PHARMACOLOGY

Ketamine Inhibits Maturation of Bone Marrow-Derived Dendritic Cells and Priming of the Th1-Type Immune Response

From the Intensive Care Unit, Osaka University Hospital, Osaka, Japan.

Address correspondence and reprint requests to Noriyuki Ohta, MD, PhD, 2-15 Yamadaoka, Suita, Osaka, Japan. Address e-mail to nohta753{at}hp-icu.med.osaka-u.ac.jp.

BACKGROUND: Dendritic cells (DCs) play a key role as antigen-presenting cells and growing evidence suggests that DCs influence T-cell activation and regulate the polarity of the immune response. Ketamine has been reported to have immunomodulatory properties that affect immune cells, including macrophages and natural killer cells. However, the effect of ketamine on DCs has not been characterized. We examined the immunomodulation of DCs by ketamine.

METHODS: We used bone marrow-derived DCs induced by granulocyte–monocyte-colony stimulating factor and interleukin (IL)-4 from bone marrow and analyzed the expression of costimulatory molecules (CD40, CD80, and CD86), major histocompatibility complex class II molecules, and secretion of IL-12p40. Furthermore, we evaluated the immune response in mixed cell cultures of DCs and T cells and the contact hypersensitivity response in a whole animal.

RESULTS: Ketamine suppressed the expression of CD40, CD80, and major histocompatibility complex class II molecules in DCs. DCs treated with ketamine also secreted less IL-12p40 and displayed greater endocytosis. In mixed cell cultures with CD4⁺ T cells and DCs, ketamine-treated DCs showed less propensity to stimulate the proliferation of CD4⁺ T cells and the secretion of interferon from CD4⁺ T cells. Furthermore, ketamine-treated DCs impaired the induction of a cell-mediated immune response.

CONCLUSION: Our findings suggest that ketamine inhibits the functional maturation of DCs and interferes with DC induction of Th1 immunity in the whole animal. These novel findings provide new insight into the immunopharmacological role of ketamine.