title: Prolonged pretreatment of mice with cholera toxin, but not isoproterenol, alleviates acute lethal systemic inflammatory response.
abstract: Isoproterenol, a synthetic non-selective β-adrenergic agonist, is often used during the immediate postoperative period after open heart surgery for its chronotropic and vasodilatory effects. It has been demonstrated that isoproterenol pretreatment followed by immediate LPS administration leads to reduced tumor necrosis factor-α (TNF-α) response in vivo. However, sepsis never happens immediately after the surgery, but rather severe immune dysfunction occurs at least 24h later. It remains elusive what effects isoproterenol might exert to innate immunity during the period. In this scenario, we investigated the effects of 24-h isoproterenol pretreatment on septic shock induced by experimental endotoxemia and bacterial peritonitis, with cholera toxin as another cAMP elevator. Unexpectedly, we found that isoproterenol and cholera toxin exhibited distinct effects in acute lethal systemic inflammatory response. Isoproterenol worsened liver injury without enhancing NK/NKT activity. Meanwhile, cholera toxin but not isoproterenol showed dramatically reduced TNF-α response in LPS induced septic shock. Our data provide a caution for the clinical use of isoproterenol and suggest that isoproterenol has cAMP-independent functions.
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China; Medical College, Nankai University, Tianjin 300071, PR China.
authors.forename: Jingyang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China; Department of Biomedicine, Institute of Frontier Medical Sciences, Jilin University, Changchun 130021, PR China.
authors.forename: Xiangrui
authors.initials: X
authors.lastname: Guo
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China.
authors.forename: Jiyan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Biomedicine, Institute of Frontier Medical Sciences, Jilin University, Changchun 130021, PR China. Electronic address: sundjjl@yahoo.com.cn.
authors.forename: Dejun
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Molecular Immunology, Institute of Basic Medical Sciences, 27 Taiping Road, Beijing 100850, PR China. Electronic address: tansun0532@163.com.
authors.forename: Qingyang
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000818:Animals; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000008:administration & dosage*; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D007545:Isoproterenol / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010538:Peritonitis / Q000517:prevention & control*; D012772:Shock, Septic / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D002772:Cholera Toxin; D000242:Cyclic AMP; D007545:Isoproterenol
keywords: Inflammatory response; Isoproterenol; Liver injury; TNF-α