Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation

Bolin Cai, Fei Chen, Yan Ji, Levente Kiss, Wouter J. de Jonge, Concepcion Conejero-Goldberg, Csaba Szabo, Edwin A. Deitch, Luis Ulloa

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Severe haemorrhage is a common cause of death despite the recent advances in critical care. Conventional resuscitation fluids are designed to re-establish tissue perfusion, but they fail to prevent inflammatory responses during resuscitation. Our previous studies indicated that the vagus nerve can modulate systemic inflammation via the alpha7 nicotinic acetylcholine receptor (α7nAchR). Here, we report that the alpha7nAChR-agonist, GTS, restrains systemic inflammation and improves survival during resuscitation. Resuscitation with GTS rescued all the animals from lethal haemorrhage in a concentration-dependent manner. Unlike conventional resuscitation fluids, GTS inhibited the production of characteristic inflammatory and cardiodepressant factors including tumour necrosis factor (TNF) and high mobility group B protein-1 (HMGB1). Resuscitation with GTS was particularly effective in restraining systemic TNF responses and inhibiting its production in the spleen. At the molecular level, GTS inhibited p65RelA but not RelB NF-κB during resuscitation. Unlike non-specific nicotinic agonists, GTS inhibited serum protein TNF levels in both normal and splenectomized, haemorrhagic animals. Resuscitation with GTS inhibited poly(ADP-ribose) polymerase and systemic HMGB1 levels. Our studies suggest that GTS provides significant advantages as compared with non-specific nicotinic agonists, and it could be a promising anti-inflammatory supplement to improve survival during resuscitation.

Original languageEnglish
Pages (from-to)3774-3785
Number of pages12
JournalJournal of Cellular and Molecular Medicine
Volume13
Issue number9 B
DOIs
Publication statusPublished - Sep 1 2009

Keywords

  • Alpha7nAchR
  • Cytokines
  • HMGB1
  • Haemorrhagic shock
  • Inflammation
  • Nicotinic receptors
  • Resuscitation
  • TNF

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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  • Cite this

    Cai, B., Chen, F., Ji, Y., Kiss, L., de Jonge, W. J., Conejero-Goldberg, C., Szabo, C., Deitch, E. A., & Ulloa, L. (2009). Alpha7 cholinergic-agonist prevents systemic inflammation and improves survival during resuscitation. Journal of Cellular and Molecular Medicine, 13(9 B), 3774-3785. https://doi.org/10.1111/j.1582-4934.2008.00550.x