- Poster presentation
Effect of the a7nAChR agonist GTS-21 on inflammation during human endotoxemia
Critical Care volume 13, Article number: P359 (2009)
Activation of the cholinergic anti-inflammatory pathway via vagus nerve stimulation or a7nAChR agonists improves outcome in animal models of endotoxemia, sepsis and experimental arthritis. This vagal anti-inflammatory pathway is mediated by the nicotinergic a7nACh receptor that can be selectively stimulated by GTS-21. Up to now, the anti-inflammatory effects of oral administration of GTS-21 in humans in vivo have not been investigated. The aim of this study was to investigate the anti-inflammatory effects of oral administration of GTS-21 on the inflammatory response in the human endotoxemia model.
We performed a double-blind placebo-controlled randomized study in 12 healthy, nonsmoking male volunteers (18 to 28 years) during experimental endotoxemia. Subjects received 150 mg GTS-21 or placebo orally three times daily 3 days before lipopolysaccharide (LPS) injection and on the day of the experiment, the last dose 1 hour before LPS administration (t = -1). One hour after the last dose of GTS-21 or placebo, LPS derived from Escherichia coli O:113 was injected (2 ng/kg intravenously).
The main study endpoint was the concentration of circulating cytokines after LPS in the absence and presence of GTS-21. The effects of GTS-21 on TNFα and IL-10 release are shown in Figures 1 and 2. There was a trend towards a decrease in TNFα levels and an increase in IL-10 levels after GTS-21 administration. A similar trend was observed in levels of other proinflammatory and anti-inflammatory cytokines.
GTS-21 suppresses TNFα and stimulates IL-10 release during human endotoxemia in healthy human volunteers, resulting in a shift towards a more anti-inflammatory pattern. This effect may have potential for in vivo modulation of the innate immune response.
About this article
Cite this article
Pompe, J., Kox, M., Hoedemaekers, C. et al. Effect of the a7nAChR agonist GTS-21 on inflammation during human endotoxemia. Crit Care 13, P359 (2009). https://doi.org/10.1186/cc7523
- Vagus Nerve
- Vagus Nerve Stimulation
- Healthy Human Volunteer
- Experimental Arthritis
- Experimental Endotoxemia