Effects of intravenous anesthetics on interleukin (IL)-6 and IL-10 production by lipopolysaccharide-stimulated mononuclear cells from healthy volunteers.

BACKGROUND: Surgical trauma has been shown to augment the plasma concentrations of proinflammatory cytokines, which are important mediators of host defense mechanisms and the systemic inflammatory response syndrome (SIRS). Recently, it has been shown that certain kinds of surgery provoke not only a proinflammatory response (SIRS) but also a concurrent anti-inflammatory response. The aim of this study was therefore to examine the effects of intravenous anesthetics on the synthesis of interleukin (IL)-6 (a proinflammatory cytokine) and IL-10 (an anti-inflammatory cytokine) by lipopolysaccharide (LPS)-stimulated mononuclear cells from healthy volunteers. METHODS: Peripheral blood mononuclear cells (PBMCs) from 17 healthy volunteers, separated by centrifugation on a Ficoll-Hypaque gradient, were washed and suspended in RPMI containing 10% heat-inactivated fetal calf serum (FCS). After adding RPMI-FCS containing various concentrations of intravenous anesthetics (propofol, thiopental, ketamine and midazolam), the PBMCs were incubated overnight in the presence of a submaximal concentration of LPS. The supernatants were collected and their IL-6 and IL-10 contents were assayed using enzyme-linked immunosorbent assay kits. RESULTS: Propofol inhibited both IL-6 and IL-10 production at 0.5 microg/mL, 5 microg/mL and 50 microg/mL. Conversely, thiopental induced IL-10 production at 2 microg/mL and 20 microg/mL. CONCLUSION: Propofol appears to inhibit both IL-6 and IL-10 production by LPS-stimulated PBMCs in vitro. Further study is required to clarify the mechanism of the suppressive effect of propofol.

[A benzodiazepine antagonist flumazenil in clinical use--a dose finding study].

The effective dose, usefulness and side effects of flumazenil, a specific benzodiazepine antagonist, have been investigated in 72 sleeping patients after the end of the surgical operation who had received flunitrazepam 0.03 mg.kg-1, a long acting benzodiazepine. The patients received intravenous injections of flumazenil 0.1 mg, 0.2 mg, 0.4 mg and 0.8 mg per person as initial doses. Four minutes after the injection of flumazenil, the percentages of the patients who were awake, were 47.4% in 0.1 mg group, 82.4% in 0.2 mg group, 82.4% in 0.4 mg group and 88.2% in 0.8 mg group respectively. There were several side effects observed in all the groups except 0.2 mg group. However, they presented no clinical problems. Therefore, flumazenil 0.2 mg as the initial dose, is considered appropriate.