Continuous administration of enteral lipid- and protein-rich nutrition limits inflammation in a human endotoxemia model.

Objective: An overzealous inflammatory response is an important cause of morbidity and mortality in surgical, trauma, and critically ill patients. Enteral administration of lipid-rich nutrition was previously shown to attenuate inflammation and reduce organ damage via a cholecystokinin-1 receptor-mediated vagovagal reflex in animal studies. The current preclinical study investigates the immunomodulatory potential of a custom-made enteral nutrition during systemic inflammation in man.

The effects of brain injury on heart rate variability and the innate immune response in critically ill patients.

Brain injury and its related increased intracranial pressure (ICP) may lead to increased vagus nerve activity and the subsequent suppression of innate immunity via the cholinergic anti-inflammatory pathway. This may explain the observed increased susceptibility to infection in these patients. In the present study, we investigated the association between brain injury, vagus nerve activity, and innate immunity.

Differential ex vivo and in vivo endotoxin tolerance kinetics following human endotoxemia.

Objectives: Endotoxin (lipopolysaccharide) tolerance is characterized by a transient refractory state to a subsequent lipopolysaccharide challenge. Following human endotoxemia, ex vivo tolerance of circulating leukocytes to lipopolysaccharide resolves within 24 hrs. However, the duration of in vivo tolerance, assumed to be primarily mediated by tissue-resident macrophages, is unknown.

Influence of different breathing patterns on heart rate variability indices and reproducibility during experimental endotoxaemia in human subjects.

HRV (heart rate variability) analysis is a widely employed method to assess cardiac autonomic nervous system activity. Accurate HRV measurement is critical to its value as a diagnostic and prognostic tool. Different breathing patterns may affect HRV, but results obtained under static conditions are conflicting.

Interplay between the acute inflammatory response and heart rate variability in healthy human volunteers.

The autonomic nervous system and the inflammatory response are intimately linked. Heart rate variability (HRV) analysis is a widely used method to assess cardiac autonomic nervous system activity, and changes in HRV indices may correlate with inflammatory markers. Here, we investigated whether baseline HRV predicts the acute inflammatory response to endotoxin.

Effects of the α7 nicotinic acetylcholine receptor agonist GTS-21 on the innate immune response in humans.

The vagus nerve can reflexively attenuate the innate immune response via binding of the vagal neurotransmitter acetylcholine (ACh) to the α7 nicotinic ACh receptor (α7nAChR). We recently reported potent anti-inflammatory effects of the α7nAChR agonist GTS-21 in human leukocytes. In the present work, we investigated the anti-inflammatory effects of GTS-21 on the innate immune response during experimental human endotoxemia.

GTS-21 inhibits pro-inflammatory cytokine release independent of the Toll-like receptor stimulated via a transcriptional mechanism involving JAK2 activation.

The vagus nerve can limit inflammation via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR). Selective pharmacological stimulation of the alpha7nAChR may have therapeutic potential for the treatment of inflammatory conditions. We determined the anti-inflammatory potential of GTS-21, an alpha7nAChR-selective partial agonist, on primary human leukocytes and compared it with nicotine, the nAChR agonist widely used for research into the anti-inflammatory effects of alpha7nAChR stimulation.