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. 2015 Sep;123(3):628-41.
doi: 10.1097/ALN.0000000000000783.

Ketamine affects in vitro differentiation of monocyte into immature dendritic cells

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Ketamine affects in vitro differentiation of monocyte into immature dendritic cells

Krzysztof Laudanski et al. Anesthesiology. 2015 Sep.

Abstract

Background: Monocytes (MOs) have the unique ability to differentiate into immature dendritic cells (iDCs) (MO→iDC) under the influence of interleukin-4 and granulocyte-monocyte colony-stimulating factor (IL-4&GM-CSF). In this study, the authors investigated the influence of ketamine on the process of MO→iDC.

Methods: iDCs were cultured from MO obtained from 36 subjects in the presence of IL-4 and GM-CSF and ketamine at 100, 10, and 1 μg/ml for 5 days. In some of the experiments, the authors used nonspecific N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, NMDA, or a neutralizing antibody for transforming growth factor β (TGFβ). The expression of surface markers and functional assays were used to assess the effect of ketamine on IL-4&GM-CSF-stimulated MO. IL-4&GM-CSF-stimulated MO's supernatants were assessed for cytokine levels.

Results: Ketamine at 10 μg/ml, and higher concentrations, diminished the expression of CD1a on IL-4&GM-CSF-stimulated MO and retarded both their ability to process DQ ovalbumin and mixed lymphocyte reaction stimulation. The addition of ketamine to IL-4&GM-CSF-differentiated MO resulted in the persistent expression of CD14 and unchanged expression of CD86 and CD206. The phagocytic abilities of IL-4&GM-CSF-differentiated MO were not changed by ketamine. MK-801, a nonselective NMDA agonist, mimicked ketamine's effect on MO→iDC differentiation. Adding exogenous NMDA to IL-4&GM-CSF-stimulated MO in the presence of ketamine partially restored the level of CD1a. TGFβ was elevated in supernatants of IL-4&GM-CSF-stimulated MO in the presence of ketamine. Adding neutralizing TGFβ antibody or TGFβR1 blocker (SB431542) resulted in the full recovery of MO→iDC, despite the presence of ketamine.

Conclusions: Ketamine diminishes the process of MO→iDC in vitro. This is mediated via NMDA-dependent mechanisms and TGFβ.

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