Influence of thiopentone and midazolam on monocyte differentiation into dendritic cells

Background

Dendritic cells (DC) play a major role in the innate immune response by directing B lymphocytes and T lymphocytes. We studied the contribution of DC to the immune suppression during thiopentone and midazolam treatment. Previous in vitro studies have shown negative effects of thiopentone on immune function [1, 2]. Clinical studies suggest that long-term sedation with thiopentone contributes to an increased incidence of nosocomial infections [3]. However, effects of thiopentone on DC have not yet been elaborated.

Materials and methods

We investigated the effects of clinical doses of thiopentone and midazolam on the differentiation of monocytes to dendritic cells in vitro. Monocytes were isolated from buffy coats of healthy donors and cultured in the presence of GM-CSF and IL-4 over 8 days. The cells were incubated with different concentrations of thiopentone and midazolam, respectively. DC were characterized through surface expression of CD1a, CD14, CD16, CD40, CD80, CD83, CD86 and HLA-DR. Cell function was quantified through FITC-dextrane phagocytosis by cytometry.

Results

In contrast to midazolam, high concentrations of thiopentone (50–100 μg/ml) led to notable alteration in the morphology and differentiation of DC. Typical morphologic characteristics like spikes and cell clustering were absent. The surface expression of CD1a was reduced by 83% (± 41%), CD40 by 93% (± 8%) and HLA-DR by 68% (± 35%). Phagocytosis capacity of these cells was decreased by 50% (± 33%).

Conclusion

We conclude that differentiation from monocytes into DC is affected by high concentrations of thiopentone but not by midazolam. This may contribute to an immune suppression during long-term thiopentone sedation.