alpha7 Nicotinic acetylcholine receptor agonist GTS-21 attenuates ventilator-induced tumour necrosis factor-alpha production and lung injury
| Autor: | Matthijs Kox, Esther Peters, J.G. van der Hoeven, Jan C. Pompe, C.W.E. Hoedemaekers, G.J. Scheffer, Michiel Vaneker, Peter Pickkers, J.A.W.M. van der Laak |
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| Rok vydání: | 2011 |
| Předmět: |
Agonist
Lipopolysaccharides Male alpha7 Nicotinic Acetylcholine Receptor medicine.drug_class Pyridines Ventilator-Induced Lung Injury Acute Lung Injury Iron metabolism Pathogenesis and modulation of inflammation [IGMD 7] Perception and Action Auto-immunity transplantation and immunotherapy [DCN 1] Nicotinic Antagonists Lung injury Pharmacology Mecamylamine Receptors Nicotinic Auto-immunity transplantation and immunotherapy [N4i 4] Benzylidene Compounds Mice GTS-21 Translational research [ONCOL 3] medicine Animals Nicotinic Agonists business.industry Tumor Necrosis Factor-alpha Pneumonia Respiration Artificial Neostigmine Interleukin-10 Pathogenesis and modulation of inflammation [N4i 1] Mice Inbred C57BL Pulmonary Alveoli Nicotinic acetylcholine receptor Anesthesiology and Pain Medicine Acetylcholinesterase inhibitor Neutrophil Infiltration Immunology Cholinergic Cholinesterase Inhibitors business medicine.drug |
| Zdroj: | British Journal of Anaesthesia, 107, 4, pp. 559-66 British Journal of Anaesthesia, 107, 559-66 |
| ISSN: | 0007-0912 |
| DOI: | 10.1093/bja/aer202 |
| Popis: | Contains fulltext : 98553.pdf (Publisher’s version ) (Open Access) BACKGROUND: Mechanical ventilation (MV) induces an inflammatory response that can lead to lung injury. The vagus nerve can limit the inflammatory response through the cholinergic anti-inflammatory pathway. We evaluated the effects of stimulation of the cholinergic anti-inflammatory pathway with the selective partial alpha7 nicotinic acetylcholine receptor (alpha7nAChR) agonist GTS-21 on inflammation and lung injury induced by MV using clinically relevant ventilator settings. Furthermore, we investigated whether altering endogenous cholinergic signalling, by administration of the non-specific nAChR antagonist mecamylamine and the peripherally acting acetylcholinesterase inhibitor neostigmine, modulates the MV-induced inflammatory response. METHODS: C57BL6 mice were injected i.p. with either the selective alpha7nAChR agonist GTS-21 (8 mg kg(-1)), the acetylcholinesterase inhibitor neostigmine (80 mug kg(-1)), the nAChR antagonist mecamylamine (1 mg kg(-1)), or a placebo; followed by 4 h of MV (8 ml kg(-1), 1.5 cm H(2)O PEEP). RESULTS: MV resulted in release of cytokines in plasma and lungs compared with unventilated mice. Lung and plasma levels of tumour necrosis factor (TNF)-alpha, but not of interleukin-10, were lower in GTS-21-treated animals compared with placebo (P |
| Databáze: | OpenAIRE |
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