{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Costantini TW"],"funding":["NIGMS NIH HHS"],"pagination":["323-329"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8792272"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["92(2)"],"pubmed_abstract":["<h4>Background</h4>The systemic inflammatory response (SIRS) drives late morbidity and mortality after injury. The α7 nicotinic acetylcholine receptor (α7nAchR) expressed on immune cells regulates the vagal anti-inflammatory pathway that prevents an overwhelming SIRS response to injury. Nonspecific pharmacologic stimulation of the vagus nerve has been evaluated as a potential therapeutic to limit SIRS. Unfortunately, the results of clinical trials have been underwhelming. We hypothesized that directly targeting the α7nAchR would more precisely stimulate the vagal anti-inflammatory pathway on immune cells and decrease gut and lung injury after severe burn.<h4>Methods</h4>C57BL/6 mice underwent 30% total body surface area steam burn. Mice were treated with an intraperitoneal injection of a selective agonist of the α7nAchR (AR-R17779) at 30 minutes postburn. Intestinal permeability to 4 kDa FITC-dextran was measured at multiple time points postinjury. Lung vascular permeability was measured 6 hours after burn injury. Serial behavioral assessments were performed to quantify activity levels.<h4>Results</h4>Intestinal permeability peaked at 6 hours postburn. AR-R17779 decreased burn-induced intestinal permeability in a dose-dependent fashion (p < 0.001). There was no difference in gut permeability to 4 kDa FITC-dextran between sham and burn-injured animals treated with 5 mg/kg of AR-R17779. While burn injury increased lung permeability 10-fold, AR-R17779 prevented burn-induced lung permeability with no difference compared with sham (p < 0.01). Postinjury activity levels were significantly improved in burned animals treated with AR-R17779.<h4>Conclusion</h4>Directly stimulating the α7nAchR prevents burn-induced gut and lung injury. Directly targeting the α7nAChR that mediates the cholinergic anti-inflammatory response may be an improved strategy compared with nonspecific vagal agonists."],"journal":["The journal of trauma and acute care surgery"],"pubmed_title":["Precision targeting of the vagal anti-inflammatory pathway attenuates the systemic inflammatory response to burn injury."],"pmcid":["PMC8792272"],"funding_grant_id":["R01 GM121530"],"pubmed_authors":["Weaver JL","Coimbra R","Costantini TW","Eliceiri BP"],"additional_accession":[]},"is_claimable":false,"name":"Precision targeting of the vagal anti-inflammatory pathway attenuates the systemic inflammatory response to burn injury.","description":"<h4>Background</h4>The systemic inflammatory response (SIRS) drives late morbidity and mortality after injury. The α7 nicotinic acetylcholine receptor (α7nAchR) expressed on immune cells regulates the vagal anti-inflammatory pathway that prevents an overwhelming SIRS response to injury. Nonspecific pharmacologic stimulation of the vagus nerve has been evaluated as a potential therapeutic to limit SIRS. Unfortunately, the results of clinical trials have been underwhelming. We hypothesized that directly targeting the α7nAchR would more precisely stimulate the vagal anti-inflammatory pathway on immune cells and decrease gut and lung injury after severe burn.<h4>Methods</h4>C57BL/6 mice underwent 30% total body surface area steam burn. Mice were treated with an intraperitoneal injection of a selective agonist of the α7nAchR (AR-R17779) at 30 minutes postburn. Intestinal permeability to 4 kDa FITC-dextran was measured at multiple time points postinjury. Lung vascular permeability was measured 6 hours after burn injury. Serial behavioral assessments were performed to quantify activity levels.<h4>Results</h4>Intestinal permeability peaked at 6 hours postburn. AR-R17779 decreased burn-induced intestinal permeability in a dose-dependent fashion (p < 0.001). There was no difference in gut permeability to 4 kDa FITC-dextran between sham and burn-injured animals treated with 5 mg/kg of AR-R17779. While burn injury increased lung permeability 10-fold, AR-R17779 prevented burn-induced lung permeability with no difference compared with sham (p < 0.01). Postinjury activity levels were significantly improved in burned animals treated with AR-R17779.<h4>Conclusion</h4>Directly stimulating the α7nAchR prevents burn-induced gut and lung injury. Directly targeting the α7nAChR that mediates the cholinergic anti-inflammatory response may be an improved strategy compared with nonspecific vagal agonists.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Feb","modification":"2025-04-05T09:06:02.882Z","creation":"2025-04-05T09:06:02.882Z"},"accession":"S-EPMC8792272","cross_references":{"pubmed":["34789702"],"doi":["10.1097/ta.0000000000003470","10.1097/TA.0000000000003470"]}}