Correspondence  |   April 2003
Thiopental and Nuclear Factor κB: Some Questions
Author Affiliations & Notes
  • Helene A. Haeberle, M.D.
  • *Tuebingen Uni-versity Hospital, Tuebingen, Germany.
Article Information
Correspondence   |   April 2003
Thiopental and Nuclear Factor κB: Some Questions
Anesthesiology 4 2003, Vol.98, 1020. doi:
Anesthesiology 4 2003, Vol.98, 1020. doi:
To the Editor:—
In their very interesting study, Loop et al.  1 demonstrate an inhibitory effect of thiopental on nuclear factor κB (NF-κB) activation in T cells.
However, we missed some essential background information in the discussion. First, the concentration of thiopental used in this study is much higher than plasma concentrations 2 noted in clinical practice or in other models presenting inhibitory effects of thiopental on interferon γ (IFN-γ) production. 3 Second, the fact that thiopental suppresses NF-κB translocation in T cells may not directly reflect general immune suppression. Regulation of cytokines in T cells is simplified in this article and may lead to false interpretation.
Therefore, it would be helpful to give some more information beyond that provided by the authors in their statement that “other transcription factors may be involved.”1 
Cytokine expression is regulated in a cell-type and stimuli-specific manner. This might explain why Loop et al.  1 were not able to demonstrate any effect of propofol on cytokine production or NF-κB activation, whereas Takaono et al.  4 describe inhibition of interleukin 6 (IL-6) production in lipopolysaccharide-stimulated peripheral blood mononuclear cells after propofol treatment. In the same study, thiopental (up to 200 μg/μl) had no significant effect on IL-6 production.
Furthermore, the ability of transcription factors to bind DNA and modulate gene transcriptions is tightly regulated in normal cells. There are four transcription factors that play a major role in the regulation of inflammatory gene expression: activator protein 1, activating transcription factor 2, signal transducers and activators of transcription, and NF-κB (and, in T cells, nuclear factor of activated T cells [NFAT]). The pattern of their activation regulates expression of inflammatory mediators. Inhibition of one transcription factor may include enhanced activation of another factor. 5 Loop et al.  1 show that thiopental reduces the production of IL-2, IL-6, and IFN-γ in phorbol-12-myristate-13-acetate–stimulated peripheral blood mononuclear cells. The authors conclude that this is due to the inhibitory effect of thiopental on NF-κB activation. However, the transcription of IL-2 and IFN-γ requires the activation of NFAT and activator protein 1 more than that of NF-κB. 6 This is of importance since NFAT is also required for transcription of IL-10, an antiinflammatory cytokine induced by thiopental. 4 In this regard it also must be mentioned that the regulation of IFN-γ seems to be different in Jurkat cells than in “normal” T cells. 7 In addition, the presentation of NFAT binding in the presence of other anesthetics would have been very interesting since it has been shown that ketamine decreases cytokine production in whole blood preparations at concentrations comparable to those used by Loop et al.  1,8 Furthermore, it has been shown that ketamine suppresses endotoxin-induced NF-κB activation in other models. 9 Therefore, it is surprising that Loop et al.  1 do not see any effect of ketamine on NF-κB activation in T cells or on cytokine production in peripheral blood mononuclear cells.
Loop T, Liu Z, Humar M, Hoetzel A, Benzing A, Pahl HL, Geiger KK, BH JP: Thiopental inhibits the activation of nuclear factor kappaB. A nesthesiology 2002; 96: 1202–13Loop, T Liu, Z Humar, M Hoetzel, A Benzing, A Pahl, HL Geiger, KK BH, JP
Turcant A, Delhumeau A, Premel-Cabic A, Granry JC, Cottineau C, Six P, Allain P: Thiopental pharmacokinetics under conditions of long-term infusion. A nesthesiology 1985; 63: 50–4Turcant, A Delhumeau, A Premel-Cabic, A Granry, JC Cottineau, C Six, P Allain, P
Salo M, Pirttikangas CO, Pulkki K: Effects of propofol emulsion and thiopentone on T helper cell type-1/type-2 balance in vitro. Anaesthesia 1997; 52: 341–4Salo, M Pirttikangas, CO Pulkki, K
Takaono M, Yogosawa T, Okawa-Takatsuji M, Aotsuka S: Effects of intravenous anesthetics on interleukin (IL)-6 and IL-10 production by lipopolysaccharide-stimulated mononuclear cells from healthy volunteers. Acta Anaesthesiol Scand 2002; 46: 176–9Takaono, M Yogosawa, T Okawa-Takatsuji, M Aotsuka, S
Jimenez JL, Punzon C, Navarro J, Munoz-Fernandez MA, Fresno M: Phosphodiesterase 4 inhibitors prevent cytokine secretion by T lymphocytes by inhibiting nuclear factor-kappaB and nuclear factor of activated T cells activation. J Pharmacol Exp Ther 2001; 299: 753–9Jimenez, JL Punzon, C Navarro, J Munoz-Fernandez, MA Fresno, M
Rao A, Luo C, Hogan PG: Transcription factors of the NFAT family: Regulation and function. Annu Rev Immunol 1997; 15: 707–47Rao, A Luo, C Hogan, PG
Sweetser MT, Hoey T, Sun YL, Weaver WM, Price GA, Wilson CB: The roles of nuclear factor of activated T cells and ying-yang 1 in activation-induced expression of the interferon-gamma promoter in T cells. J Biol Chem 1998; 273: 34775–83Sweetser, MT Hoey, T Sun, YL Weaver, WM Price, GA Wilson, CB
Kawasaki T, Ogata M, Kawasaki C, Ogata J, Inoue Y, Shigematsu A: Ketamine suppresses proinflammatory cytokine production in human whole blood in vitro. Anesth Analg 1999; 89: 665–9Kawasaki, T Ogata, M Kawasaki, C Ogata, J Inoue, Y Shigematsu, A
Sakai T, Ichiyama T, Whitten CW, Giesecke AH, Lipton JM: Ketamine suppresses endotoxin-induced NF-kappaB expression. Can J Anaesth 2000; 47: 1019–24Sakai, T Ichiyama, T Whitten, CW Giesecke, AH Lipton, JM