Authors:
R. E. BundySection of Anaesthetics, Pain Medicine and Critical Care, Department of Surgery and Cancer, Imperial College London, Heart Science Centre, Harefield Hospital, UB9 6JH, Harefield, UK

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B. FalusiDepartment of Anaesthesiology and Intensive Care, University of Pécs, H-7624, Pécs, Hungary

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Nandor MarczinSection of Anaesthetics, Pain Medicine and Critical Care, Department of Surgery and Cancer, Imperial College London, Heart Science Centre, Harefield Hospital, UB9 6JH, Harefield, UK

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Abstract

Thiopental (TP) along with being an intravenous anaesthetic is frequently used in high doses to treat increased intracranial hypertension. Long-term treatments result in its accumulation in the lungs and an increased incidence of nosocomial infections. Since TP has been shown to modulate TNF-induced inflammatory pathways in lymphocytes, we hypothesised that TP may modulate pro-inflammatory events in human pulmonary epithelial cells. We investigated the potential influence of TP on MAPK and NF-κB signal transduction pathways in the absence and presence of TNF. TP at 1 mg/ml concentrations produced a 10-fold increase in p38 activation as assessed by Western blotting using monoclonal antibodies specific for double phosphorylated, thereby activated form of p38. This increase in p38 MAPK phosphorylation was evident as early as 10 minutes (4.5-fold), peaked at 60 minutes (11.3-fold) with return towards baseline (3.6-fold) in 2 hours. This response was specific for p38, since there was no evidence for activation of NF-κB pathway by TP as judged from Western blot analysis of steady-state IκB levels. TNF activated both p38 (2.4–11.4-fold increases) and depleted IκB (64–35% of control) in a concentration dependent manner (0.1–10 ng/ml). Interestingly, in the presence of TP, TNF did not produce a further increase in p38 activation. In addition, TP tended to attenuate TNF-induced NF-κB activation. These data suggest that high dose TP has the capacity to specifically alter p38MAPK activation and to modulate TNF signalling in epithelial cells, which might have implications to immunological responses in the lung.

  • 1. M. Keel L. Mica J. Stover R. Stocker O. Trentz L. Härter 2005 Thiopental-induced apoptosis in lymphocytes is independent of CD95 activation Anesthesiology 103 576 584.

    • Search Google Scholar
    • Export Citation
  • 2. W. Schalen K. Messeter C.H. Nordstorm 1992 Complications and side effects during thiopentone therapy in patients with severe head injury Acta Anaesthesiol Scand 36 369 377.

    • Search Google Scholar
    • Export Citation
  • 3. T. Loop Z. Liu M. Humar A. Hoetzel A. Benzing H.L. Pahl K.K. Geiger B.H. Pannen 2002 Thiopental inhibits the activation on nuclear factor B Anesthesiology 96 1202 1213.

    • Search Google Scholar
    • Export Citation
  • 4. K.E. Eberhardt B.M. Thimm A. Spring W.R. Maskos 1992 Dose d-dependent rate of nosocomial pulmonary infection in mechanically ventilated patients with brain oedema receiving barbiturates: Prospective case study Infection 20 12 18.

    • Search Google Scholar
    • Export Citation
  • 5. T. Yasuda T. Yamaba K. Sawazaki F. Masuyama D. Nadano H. Takeshita K. Kishi 1993 Postmortem concentrations of thiopental in tissues: A sudden death case Int J LegalMed 105 239 241.

    • Search Google Scholar
    • Export Citation
  • 6. R. Sen D. Baltimore 1986 Multiple nuclear factors interact with the immunoglobulin enhancer sequences Cell 46 705 716.

  • 7. H.K. Pahl 1999 Activators and target genes of Rel/NF-κB transcription factors Oncogene 18 6853 6866.

  • 8. N.D. Perkins 2007 Integrating cell-signalling pathways with NF-κB and IKK function Nat Rev Mol Cell Biol 8 49 62.

  • 9. T. Loop M. Humar S. Pischke A. Hoetzel R. Schmidt H.L. Pahl K.K. Geiger B.H.J. Pannen 2003 Thiopental inhibits tumor necrosis factor α-induced activation of nuclear factor κB through suppression of IκB kinase activity Anesthesiology 99 360 367.

    • Search Google Scholar
    • Export Citation
  • 10. C. Dong R.J. Davis R.A. Flavell 2002 MAP kinases in the immune response Annu Rev Immunol 20 55 72.

  • 11. M. Humar N. Andriopoulos S.E. Pischke T. Loop R. Schmidt A. Hoetzel M. Roesslein H.L. Pahl K.K. Geiger B.H.J. Pannen 2004 Inhibition of activator protein 1 by barbiturates is mediated by differential effects on mitogen-activated protein kinases and the small G proteins Ras and Rac-1 J Pharmacol Exp Ther 311 1232 1240.

    • Search Google Scholar
    • Export Citation
  • 12. I. Roberts 2001 Barbiturates for Acute Traumatic Brain Injury Update Software The Cochrane Library, Issue 2 Oxford.

  • 13. J. Ghajar R.J. Hariri R.K. Narayan L.A. Iacono K. Firlik R.H. Patterson 1995 Survey of critical care management of comatose, head-injured patients in the United States Crit Care Med 23 560 567.

    • Search Google Scholar
    • Export Citation
  • 14. C. De Deyne R. De Jongh 2000 Euro-Neuro 1998 survey on the management of severe head injury Eur J Anaesthesiol 17 3 5.

  • 15. J.F. Stover R. Stocker 1998 Barbiturate coma may promote reversible bone marrow suppression in patients with severe isolated traumatic brain injury Eur J Clin Pharmacol 54 529 534.

    • Search Google Scholar
    • Export Citation
  • 16. A.H. Hsieh M.J. Bishop P.S. Kubilis D.W. Newell D.J. Pierson 1992 Pneumonia following closed head injury Am Rev Respir Dis 146 290 294.

    • Search Google Scholar
    • Export Citation
  • 17. K. Ishikawa H. Tanaka M. Takaoka H. Ogura T. Shiozaki H. Hosotsubo T. Shimazu T. Yoshioka H. Sugimoto 1999 Granulocyte colonystimulating factor ameliorates life-threatening infections after combined therapy with barbiturates and mild hypothermia in patients with severe head injuries J Trauma 46 999 1007.

    • Search Google Scholar
    • Export Citation
  • 18. P. Nadal J.M. Nicolas C. Font A. Vilella S. Nogue 1995 Pneumonia in ventilated head trauma patients: The role of thiopental therapy Eur J Emerg Med 2 14 16.

    • Search Google Scholar
    • Export Citation
  • 19. N. Marczin R.E. Bundy G.S. Hoare M. Yacoub 2003 Redox regulation following cardiac ischemia and reperfusion Coron Artery Dis 14 123 133.

    • Search Google Scholar
    • Export Citation
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2019  
Scimago
H-index
11
Scimago
Journal Rank
0,220
Scimago
Quartile Score
Medicine (miscellaneous) Q3
Scopus
Cite Score
155/133=1,2
Scopus
Cite Score Rank
General Medicine 199/529 (Q2)
Scopus
SNIP
0,343
Scopus
Cites
206
Scopus
Documents
23

 

Interventional Medicine and Applied Science
Language English
Size  
Year of
Foundation
2009
Publication
Programme
changed title
Volumes
per Year
 
Issues
per Year
 
Founder Akadémiai Kiadó
Founder's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 2061-1617 (Print)
ISSN 2061-5094 (Online)

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