BACKGROUND: During @entity1661 , the inhibition of gastrointestinal (GI) motility together with mucosal barrier dysfunction will lead to increased bacterial translocation and maintenance of @entity295 . The activation of the vagal anti-inflammatory pathway remains an appealing therapeutic strategy in @entity295 . In this respect, selective @entity15683 nicotinic @entity934 receptor (a7nAChR) agonists have shown anti-inflammatory properties in several animal models of @entity32 . METHODS: @entity295 was induced in OF-1 @entity19 by cecal ligation and puncture (CLP). GI transit was quantified, and cytokine levels were determined in serum and colon. Colonic permeability was assessed by means of Evans blue injection. We studied the effect of @entity18686 , an a7nAChR agonist, on the aforementioned parameters. Splenectomized animals as well as a7nAChR-knock-out animals ( @entity15683 ) were included to study the role of splenic macrophages and the a7nAChR during polymicrobial @entity1661 . RESULTS: In septic animals, @entity18686 significantly @entity344 , lowered systemic and colonic levels of @entity777 , decreased colonic permeability, and decreased the number of positive cultures obtained from blood and mesenteric lymph nodes. Splenectomy prevented animals from developing @entity295 -induced @entity2616 . @entity15683 @entity19 displayed a more severe septic phenotype, whereas @entity18686 remarkably was also beneficial in these animals. CONCLUSION: Our results show that peripheral targeting of the vagal anti-inflammatory pathway proves beneficial in an animal model of polymicrobial @entity1661 . A major role is allocated to splenic immune cells in the development of @entity295 , as preventive splenectomy was protective for the development of @entity295 . Data on the @entity15683 @entity19 suggest that the beneficial effects mediated by @entity18686 on @entity32 and motility might be related to activation of other receptors besides the a7nAChR.

EFFECT OF XXXX , AN @entity15683 NICOTINIC ACETYLCHOLINE RECEPTOR AGONIST, ON CLP-INDUCED INFLAMMATORY, GASTROINTESTINAL MOTILITY, AND COLONIC PERMEABILITY CHANGES IN @entity19 .

@entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity295 :: ('MESH:D018805', 'Disease') :: ['sepsis', 'Sepsis'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity18686 :: ('MESH:C088936', 'Chemical') :: ['GTS-21'] @entity2616 :: ('MESH:D045823', 'Disease') :: ['ileus'] @entity1661 :: ('MESH:D000008', 'Disease') :: ['abdominal sepsis'] @entity344 :: ('MESH:D005767', 'Disease') :: ['ameliorated GI motility'] @entity777 :: ('16193(Tax:10090)', 'Gene') :: ['IL-6'] @entity15683 :: ('11441(Tax:10090)', 'Gene') :: ['Chrna7', 'alpha7'] @entity934 :: ('MESH:D000109', 'Chemical') :: ['acetylcholine']
@entity18686 :: (MESH:C088936,Chemical) :: ['GTS-21']
