Thiopental inhibits migration of human leukocytes through human endothelial cell monolayers in vitro

Hofbauer, Roland; Salfinger, Heribert; Kapiotis, Stylianos; Moser, Doris; Frass, Michael

doi:10.1007/s001340050698

Cited by 6 publications

(2 citation statements)

References 20 publications

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“…This means that leucocyte migration had occurred already at the 4 h point into the wound in spite of surgery and balanced anaesthesia, since normal tissues do not contain leucocytes. Previous studies in adults have shown that anaesthetics can reduce leucocyte migration rate in vitro , and major surgery leads to increased leucocyte adherence, decreased neutrophil chemotaxis and dimished neutrophil delivery to areas of inflammation in adults ( 9,10), but that has not been tested earlier in small children.…”

Section: Discussionmentioning

confidence: 99%

Local and systemic immune response to surgery under balanced anaesthesia in children

Mattila-Vuori¹,

Salo²,

Iisalo

et al. 2000

Pediatric Anesthesia

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We studied perioperative changes in the immune response and compared changes in the peripheral blood with those in the wound in 20 boys (0.5-3 years) during elective inguinal surgery under balanced anaesthesia. Blood samples were drawn before premedication, immediately, and 4 or 24 h after anaesthesia. Cells from the wound were harvested with the Cellstick device, removed from the wound 4 (n=10) or 24 h (n=10) after anaesthesia. We found decreased lymphocyte counts in the peripheral blood, increased percentages of activated T lymphocytes and B lymphocytes, and decreased percentages of total T lymphocytes, T helper cells and T cytotoxic cells. The percentages of T helper cells and B lymphocytes were lower in the wound than in blood. Mitogen-induced lymphocyte proliferative responses decreased. This study demonstrates perioperative changes in the immune response in children and, as a new finding, that immune effector cells in the blood and in the wound are in a dynamic balance.

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Section: Discussionmentioning

confidence: 99%

Local and systemic immune response to surgery under balanced anaesthesia in children

Mattila-Vuori¹,

Salo²,

Iisalo

et al. 2000

Pediatric Anesthesia

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“…During T cell activation, the actin cytoskeleton permits the formation of immune synapses and scaffolds for signal transduction molecules (Grakoui et al, 1999;Dustin and Cooper, 2000). Indeed, barbiturate application affects the microtubular assembly (Ventilla and Brown, 1976), and multiple reports describe reduced neutrophil chemotaxis or leukocyte migration through human endothelial cell monolayers following barbiturate exposure (Hofbauer et al, 1998;Nishina et al, 1998). Our results suggest that barbiturates directly affect these processes on the level of rac-1, whereas thiopental interacts differently.…”

Section: Discussionmentioning

confidence: 54%

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

Humar¹,

Andriopoulos²,

Pischke³

et al. 2004

J Pharmacol Exp Ther

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Barbiturates are known to suppress protective immunity, and their therapeutic use is associated with nosocomial infections. Although barbiturates inhibit T cell proliferation, differentiation, and cytokine synthesis, only thiobarbiturates markedly reduce the activation of immune regulatory transcription factors such as nuclear factor-B and nuclear factor of activated T cells. In this study, we investigated barbiturate-mediated effects on the regulation of the transcription factor activator protein 1 (AP-1) in primary T lymphocytes. We show that both thiobarbiturates and their oxy-analogs inhibit AP-1-dependent gene expression and AP-1 complex formation at clinically relevant doses. Furthermore, mitogen-activated protein (MAP) kinase activity, which transcriptionally and posttranslationally regulates AP-1 complex formation, is suppressed by most barbiturates. CD3/ CD28-or phorbol 12-myristate 13-acetate (PMA)/ionomycininduced p38 and extracellular signal-regulated kinase 1/2 phosphorylation or c-jun NH 2 -terminal kinase (JNK) 1/2 kinase activity was significantly diminished by pentobarbital, thiamylal, secobarbital, or methohexital treatment. These barbiturates also inhibited the initiators of the MAP kinase cascade, the small G proteins ras and rac-1, and prevented binding to their partners raf-1 and PAK, respectively. Thiopental, unlike the other barbiturates, only reduced ras and JNK activity upon direct CD3/CD28 receptor engagement. Contrarily, upon PMA/ ionomycin stimulation, thiopental blocked AP-1-dependent gene expression independently of the small G protein ras and MAP kinases, thus suggesting an additional, unknown mechanism of AP-1 regulation. In conclusion, our results contribute to the explanation of a clinically manifested immune suppression in barbiturate-treated patients and support the idea of a MAP kinase-independent regulation of AP-1 by PKC and calcium in human T cells.

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The Immunomodulatory Effects of Anesthetic and Analgesic Agents

Kummer¹,

Netto²,

Marshall³

2002

Intensive Care Medicine

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Thiopental inhibits migration of human leukocytes through human endothelial cell monolayers in vitro

Abstract: In conclusion, we could show that thiopental is able to reduce the migration of PMNL through ECM significantly.

Cited by 6 publications

References 20 publications

Local and systemic immune response to surgery under balanced anaesthesia in children

Local and systemic immune response to surgery under balanced anaesthesia in children

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

The Immunomodulatory Effects of Anesthetic and Analgesic Agents

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