Attenuation of catecholamine-induced immunosuppression in whole blood from patients with sepsis
Attenuation of catecholamine-induced immunosuppression in whole blood from patients with sepsis
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DOI：
10.1097/00024382-199912000-00002
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发表时间：
1999-12-01
期刊：
影响因子：
3.1
通讯作者：
Függer, R
中科院分区：
文献类型：
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作者：
Bergmann, M;Gornikiewicz, A;Függer, R
对健康志愿者进行的研究表明，儿茶酚胺下调脂多糖（LPS）诱导的肿瘤坏死因子(TNF) α、白细胞介素(IL)-6和IL-1 β的产生。我们扩展了这一观察结果，并表明这种效应是基于这些细胞因子mRNA浓度的变化，儿茶酚胺在严重败血症中由于内源性产生而增加，当疾病发展到长期低血压状态时，必须外源性给予。我们在这里研究儿茶酚胺的免疫调节作用是否也可以在长期严重脓毒症患者和长期脓毒症休克患者的血液中被证明。体外用LPS刺激血液，在肾上腺素存在和不存在的情况下，测定细胞因子蛋白浓度。在健康志愿者的血液中，肾上腺素使lps刺激的TNF α合成减少62.5% (P < 0.0001)， IL-6合成减少39% (P < 0.0001)， IL-1 β合成减少40% (P = 0.015)，使lps刺激的IL-10合成增加77.8% （P < 0.0001）。相应的，在长期严重脓毒症患者的血液中，TNF α降低67.2% (P < 0.0001)， IL-6降低32.9% (P < 0.0001)；这些患者的IL-lp和IL-10不受儿茶酚胺的调节。在脓毒性休克患者的血液样本中，肾上腺素没有调节IL-6和IL-10的细胞因子水平，仅降低了36.4%的TNF - α (P < 0.0001)。有趣的是，在脓毒性休克患者的血液中，肾上腺素抑制了73%的IL-1 β的产生（P < 0.0001），这是健康志愿者血液样本的两倍。脓毒性血液对儿茶酚胺反应的改变可能是由于长期疾病中白细胞反应性的改变，尽管不能完全排除先前存在的儿茶酚胺的额外作用。
Studies performed on healthy volunteers have revealed that catecholamines down-regulate the lipopolysaccharide (LPS)-induced production of tumor necrosis factor (TNF)alpha, interleukin (IL)-6, and IL-1 beta. We extended this observation and show that this effect is based on changes in the mRNA concentration of these cytokines, Catecholamines are increased in severe sepsis due to endogenous production and have to be administered exogenously when the disease has proceeded to the state of prolonged hypotension. We here investigated whether the immunomodulating effect of catecholamines could also be demonstrated in the blood of patients with prolonged severe sepsis and of those in prolonged septic shock. Blood was stimulated ex vivo with LPS in the presence and absence of epinephrine and the cytokine protein concentration was determined. In blood of healthy volunteers, epinephrine reduced the LPS-stimulated synthesis of TNF alpha by 62.5% (P < 0.0001), of IL-6 by 39% (P < 0.0001), and of IL-1 beta by 40% (P = 0.015), and increased the LPS-stimulated IL-10 production by 77.8% (P < 0.0001). Correspondingly, in blood of patients with prolonged severe sepsis, TNF alpha was reduced by 67.2% (P < 0.0001) and IL-6 was reduced by 32.9% (P < 0.0001); IL-lp and IL-10 were not modulated by catecholamines in these patients. In blood samples of patients in prolonged septic shock, epinephrine did not modulate cytokine levels of IL-6 and IL-10, and decreased TNF alpha only by 36.4% (P < 0.0001). Interestingly, epinephrine suppressed the IL-1 beta production by 73% (P < 0.0001) in blood of patients in prolonged septic shock, which was twice as much as in blood samples of healthy volunteers. The altered response of septic blood to catecholamines might be due to an altered reactivity of leukocytes in the prolonged disease although an additional role of preexisting catecholamines cannot be completely excluded.