Prolonged pretreatment of mice with cholera toxin,but not isoproterenol,alleviates acute lethal systemic inflammatory response

【作者】 汪静洋； 郭祥瑞； 王庆阳； 孙德军； 张纪岩；

【机构】 军事医学科学院； 吉林大学；

【摘要】 Isoproterenol,a synthetic non-selectiveβ-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 least24 hours later.It remains elusive what effects isoproterenol might exert to innate immunity during the period.In this scenario,we investigated the effects of 24 hour-isoproterenol pretreatment on septic shock induced by experimental endotoxernia and bacterial peritonitis,with cholera toxin(CTX)as another cAMP elevator.Unexpectedly,we found isoproterenol and CTX exhibited distinct effects in acute lethal systemic inflammatory response.Isoproterenol worsened liver injury without enhancing NK/NKT activity.Meanwhile,CTX but not isoproterenol showed dramatically reduced TNF-αresponse in LPS induced septic shock.Our data provide a caution for the clinical use of isoproterenol and suggest that isoproterenol has cAMP-independent functions.更多还原

【Abstract】 Isoproterenol,a synthetic non-selective p-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-a(TNF-α) response in vivo.However,sepsis never happens immediately after the surgery,but rather severe immune dysfunction occurs at least24 hours later.It remains elusive what effects isoproterenol might exert to innate immunity during the period.In this scenario,we investigated the effects of 24 hour-isoproterenol pretreatment on septic shock induced by experimental endotoxemia and bacterial peritonitis,with cholera toxin(CTX) as another cAMP elevator.Unexpectedly,we found isoproterenol and CTX exhibited distinct effects in acute lethal systemic inflammatory response.Isoproterenol worsened liver injury without enhancing NK/NKT activity.Meanwhile,CTX but not isoproterenol showed dramatically reduced TNFa 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.更多还原