Effects of a peripheral cholinesterase inhibitor on cytokine production and autonomic nervous activity in a @entity35 model of XXXX .

@entity295 @entity326 @entity935 @entity13358 @entity568 @entity36726 @entity2922 @entity35 @entity2661 @entity1063
PURPOSE: Recently, cholinergic anti-inflammatory pathway manipulation has been proposed as a new strategy to control cytokine production in @entity295 . We investigated whether hypercytokinemia can be controlled via this pathway in an animal model of @entity295 , with concomitant monitoring of autonomic nervous activity involving heart rate variability (HRV) analysis of electrocardiographic R-R intervals. METHODS: Sixty-eight adult male @entity35 were used (28 for examination of cytokine production and autonomic nervous activity; 40 for survival analysis). Each part of the study involved four animal groups, including two control groups without drug administration. @entity295 was induced by cecal ligation and puncture (CLP). @entity36726 , a peripheral, non-selective cholinesterase inhibitor (0.01mg/kg), was administered subcutaneously 90 min after surgery. Continuous electrocardiograms were recorded for 5 min before and after surgery (at intervals of 5h) in CLP and sham-operated animals for HRV analysis. Blood samples were collected 20 h after surgery for serum cytokine and @entity2922 assay. RESULTS: On HRV analysis, @entity36726 inhibited reduction of total power and high-frequency components in CLP animals (P<0.05). @entity36726 significantly inhibited cytokine induction ( @entity568 and @entity13358 ) (P<0.01) as well as increase in serum levels of @entity1063 and @entity935 (P<0.05). @entity36726 did not significantly improve CLP animal survival rate. CONCLUSIONS: The cholinesterase inhibitor @entity36726 inhibited induction of inflammatory cytokines and @entity2661 as well as HRV suppression in a @entity35 CLP model, suggesting that an agent modulating the cholinergic anti-inflammatory pathway can control excess cytokine production involved in the pathogenesis of severe @entity295 / @entity326 .
