title: A subanesthetic dose of isoflurane during postconditioning ameliorates zymosan-induced neutrophil inflammation lung injury and mortality in mice.
abstract: Anesthetic isoflurane (ISO) has immunomodulatory effects. In the present study, we investigated whether a subanesthetic dose of ISO (0.7%) protected against zymosan (ZY) induced inflammatory responses in the murine lung and isolated neutrophils. At 1 and 6 hrs after ZY administration intraperitoneally, ISO was inhaled for 1 hr, and 24 hrs later, lung inflammation and injury were assessed. We found that ISO improved the survival rate of mice and mitigated lung injury as characterized by the histopathology, wet-to-dry weight ratio, protein leakage, and lung function index. ISO significantly attenuated ZY-induced lung neutrophil recruitment and inflammation. This was suggested by the downregulation of (a) endothelial adhesion molecule expression and myeloperoxidase (MPO) activity in lung tissue and polymorphonuclear neutrophils (b) chemokines, and (c) proinflammatory cytokines in BALF. Furthermore, ZY-induced nuclear translocation and DNA-binding activity of NF- κ B p65 were also reduced by ISO. ISO treatment inhibited iNOS expression and activity, as well as subsequent nitric oxide generation. Consistent with these in vivo observations, in vitro studies confirmed that ISO blocked NF- κ B and iNOS activation in primary mouse neutrophils challenged by ZY. These results provide evidence that 0.7% ISO ameliorates inflammatory responses in ZY-treated mouse lung and primary neutrophils.
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Nan-lin
authors.initials: NL
authors.lastname: Li
authors.affiliation: Institute of Anal-Colorectal Surgery, No. 150 Central Hospital of PLA, Luoyang, Henan 451000, China ; Department of Immunology, State Key Laboratory of Cancer Biology, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Jun-tang
authors.initials: JT
authors.lastname: Li
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Shi-fang
authors.initials: SF
authors.lastname: Yuan
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yi
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Jiang-hao
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Yong-gang
authors.initials: YG
authors.lastname: Lv
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Yu-cai
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Vascular and Endocrine Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710032, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ling
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000473:pathology; D007530:Isoflurane / Q000008:administration & dosage*; D008168:Lung / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D011014:Pneumonia / Q000188:drug therapy*; D013997:Time Factors; D015054:Zymosan / Q000009:adverse effects*
chemical_list: D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; D009573:Nitrites; D015054:Zymosan; D007530:Isoflurane; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse