T. Loop, Zhihen Liu, M. Humar
May 1, 2002
Citations
1
Influential Citations
61
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Quality indicators
Journal
Anesthesiology
Abstract
Background Thiopental is frequently used for the treatment of intracranial hypertension after severe head injury. Its long-term administration increases the incidence of nosocomial infections, which contributes to the high mortality rate of these patients. However, the mechanism of its immunosuppressing effect remains unknown. Methods The effect of thiopental (200–1000 &mgr;g/ml) on the activation of the nuclear transcription factor &kgr;B (NF-&kgr;B; electrophoretic mobility shift assays), on NF-&kgr;B–driven reporter gene activity (transient transfection assays), on the expression of NF-&kgr;B target genes (enzyme-linked immunoassays), on T-cell activation (flow cytometric analyses of CD69 expression), and on the content of the NF-&kgr;B inhibitor I&kgr;B-&agr; (Western blotting) was studied in human T lymphocytes in vitro. Results Thiopental inhibited the activation of the transcription factor NF-&kgr;B but did not alter the activity of the cyclic adenosine monophosphate response element binding protein. Other barbiturates (methohexital), anesthetics (etomidate, propofol, ketamine), or opioids (fentanyl, morphine) did not affect NF-&kgr;B activation. Thiopental-mediated suppression of NF-&kgr;B could be observed in Jurkat cells and in primary CD3+ lymphocytes from healthy volunteers, was time- and concentration-dependent, occurred at concentrations that are clinically achieved, and persisted for hours after the incubation. It was associated with an inhibition of NF-&kgr;B–driven reporter gene activity, of the expression of interleukin-2, -6, and -8, and interferon &ggr;, and of the activation of CD3+ lymphocytes. Suppression of NF-&kgr;B appeared to involve reduced degradation of I&kgr;B-&agr;. Conclusion The results demonstrate that thiopental inhibits the activation of NF-&kgr;B and may thus provide a molecular mechanism for some of the immunosuppressing effects associated with thiopental therapy.