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experiments were approved by and performed under guidelines of the ethical committee for use of animals , barts and the london school of medicine and home office regulations ( guidance on the operation of animals , scientific procedures act , 1986 ) .
ivm was used to observe actions of rvd2 on platelet activating factor ( paf ; c16 form : c26h54no7p ; 100 nm ; sigma ( 1h prior to rvd2;time 0 ) ) -stimulated leukocyte responses within the cremasteric microcirculation of c57 bl/6 mice .
mice were anesthetized with xylazine ( 7.5 mg / kg ) and ketamine ( 150 mg / kg ) , and cremaster prepared29 . in some experiments , fitc - albumin ( 1 mg )
clp was performed in male fvb mice16 , in accordance with the harvard medical area standing committee on animals protocol # 02570 .
a through and through puncture was performed with a 20 gauge needle , followed by one additional puncture in the distal tip of the cecum .
administration of vehicle ( 0.1% ethanol ) , or rvd2 methyl ester ( 100 ng ) at the time of puncture .
at 12h , rectal temperature was measured , blood collected by cardiac puncture and peritoneal exudates obtained .
plasma and peritoneal cytokine levels were determined by searchlight array ( woburn , ma ) .
multiple group comparisons were made using one - way or two - way anova followed by dunnett s or bonferroni post tests where appropriate and direct comparisons made using a two - tailed unpaired student s t - test .
kaplan - meier survival curves were analyzed using a one - tailed log - rank test . in all cases ,
experiments were approved by and performed under guidelines of the ethical committee for use of animals , barts and the london school of medicine and home office regulations ( guidance on the operation of animals , scientific procedures act , 1986 ) .
ivm was used to observe actions of rvd2 on platelet activating factor ( paf ; c16 form : c26h54no7p ; 100 nm ; sigma ( 1h prior to rvd2;time 0 ) ) -stimulated leukocyte responses within the cremasteric microcirculation of c57 bl/6 mice .
mice were anesthetized with xylazine ( 7.5 mg / kg ) and ketamine ( 150 mg / kg ) , and cremaster prepared29 . in some experiments , fitc - albumin ( 1 mg )
clp was performed in male fvb mice16 , in accordance with the harvard medical area standing committee on animals protocol # 02570 .
a through and through puncture was performed with a 20 gauge needle , followed by one additional puncture in the distal tip of the cecum .
administration of vehicle ( 0.1% ethanol ) , or rvd2 methyl ester ( 100 ng ) at the time of puncture . in some experiments , rvd2-me ( 1 g ) was administered i.p .
plasma and peritoneal cytokine levels were determined by searchlight array ( woburn , ma ) .
multiple group comparisons were made using one - way or two - way anova followed by dunnett s or bonferroni post tests where appropriate and direct comparisons made using a two - tailed unpaired student s t - test .
kaplan - meier survival curves were analyzed using a one - tailed log - rank test . in all cases ,
a growing body of evidence indicates that resolution of acute inflammation is an active process1,2 . 
 resolvins are a new family of lipid mediators enzymatically generated within resolution networks that possess unique and specific functions to orchestrate catabasis2,3 . 
 resolvin d2 ( rvd2 ) was originally identified in resolving exudates , yet its individual contribution in resolution remained to be elucidated . here , we established rvd2 s potent stereoselective actions in reducing excessive neutrophil trafficking to inflammatory loci 
 . rvd2 decreased leukocyte : endothelial interactions in vivo by endothelial - dependent nitric oxide production , and direct modulation of leukocyte adhesion receptor expression . in microbial sepsis initiated by cecal ligation and puncture ( clp ) , 
 rvd2 sharply decreased both local and systemic bacterial burden , excessive cytokine production and neutrophil recruitment , while increasing peritoneal mononuclear cells and macrophage phagocytosis . 
 these multi - level pro - resolving actions of rvd2 translate to increased survival from clp - induced sepsis and surgery . 
 together , these results identify rvd2 as a potent endogenous regulator of excessive inflammatory responses that acts via multiple cellular targets to stimulate resolution and preserve immune vigilance .