Oberbeck Reiner, Schmitz Daniel, Wilsenack Klaus, Schüler Marc, Pehle Birthe, Schedlowski Manfred, Exton Michael S
Department of Trauma Surgery, University Hospital of Essen, Essen, Germany.
Neuroimmunomodulation. 2004;11(4):214-23. doi: 10.1159/000078439.
An immunomodulatory effect of epinephrine has been reported that is supposed to be mediated via beta-adrenergic receptors. The effect of epinephrine and/or beta-adrenergic blockade on cellular immune functions during systemic inflammation has not yet been investigated.
Male NMRI mice were treated with either an infusion of epinephrine (0.05 mg/kg/h i.p.), administration of the nonselective beta-adrenoceptor antagonist propranolol (0.5 mg/kg s.c.), or a combination of epinephrine and propranolol after induction of a polymicrobial sepsis by cecal ligation and puncture. Forty-eight hours thereafter survival and cellular immune functions (splenocyte proliferation, splenocyte apoptosis and cytokine release, distribution of leukocyte subsets) were determined.
Infusion of epinephrine did not affect lethality of septic mice but induced alterations of splenocyte apoptosis, splenocyte proliferation and IL-2 release and was associated with profound changes of circulating immune cell subpopulations. Treatment with propranolol augmented the epinephrine-induced increase of splenocyte apoptosis, did not affect the decrease of splenocyte proliferation and IL-2 release, augmented the release of IL-6 and antagonized the mobilization of natural killer cells observed in epinephrine-treated animals. Furthermore, these immunologic alterations were accompanied by a significant increase of sepsis-induced mortality. Coadministration of propranolol and epinephrine augmented the propranolol-induced changes of splenocyte apoptosis and IL-6 release and was associated with the highest mortality of septic mice.
Epinephrine infusion modulated cellular immune functions during systemic inflammation without an impact on survival. A pharmacologic beta-adrenergic blockade partly augmented the epinephrine-induced immune alterations and was associated with a pronounced increase of mortality. This effect was further augmented by a combination of epinephrine infusion and beta-adrenergic blockade. These data indicate that adrenergic mechanisms modulate cellular immune functions and survival during sepsis, with these effects being mediated via alpha- and beta-adrenergic pathways.
已有报道称肾上腺素具有免疫调节作用，推测其通过β - 肾上腺素能受体介导。然而，肾上腺素和/或β - 肾上腺素能阻滞剂对全身炎症期间细胞免疫功能的影响尚未得到研究。
通过盲肠结扎和穿刺诱导多微生物败血症后，雄性NMRI小鼠分别接受肾上腺素输注（0.05毫克/千克/小时，腹腔注射）、非选择性β - 肾上腺素能受体拮抗剂普萘洛尔给药（0.5毫克/千克，皮下注射）或肾上腺素与普萘洛尔联合治疗。48小时后，测定生存率和细胞免疫功能（脾细胞增殖、脾细胞凋亡和细胞因子释放、白细胞亚群分布）。
输注肾上腺素不影响败血症小鼠的致死率，但诱导脾细胞凋亡、脾细胞增殖和白细胞介素 - 2释放发生改变，并与循环免疫细胞亚群的显著变化有关。普萘洛尔治疗增强了肾上腺素诱导的脾细胞凋亡增加，不影响脾细胞增殖和白细胞介素 - 2释放的减少，增强了白细胞介素 - 6的释放，并拮抗了肾上腺素治疗动物中观察到的自然杀伤细胞动员。此外，这些免疫改变伴随着败血症诱导死亡率的显著增加。普萘洛尔和肾上腺素联合给药增强了普萘洛尔诱导的脾细胞凋亡和白细胞介素 - 6释放的变化，并与败血症小鼠的最高死亡率相关。
输注肾上腺素在全身炎症期间调节细胞免疫功能，但对生存率无影响。药理学上的β - 肾上腺素能阻滞部分增强了肾上腺素诱导的免疫改变，并与死亡率的显著增加有关。肾上腺素输注和β - 肾上腺素能阻滞联合使用进一步增强了这种效应。这些数据表明，肾上腺素能机制在败血症期间调节细胞免疫功能和生存率，这些效应通过α - 和β - 肾上腺素能途径介导。
