JAMA:脓毒症死亡者 免疫强化治疗对其有效
2012-01-01 MedSci原创 MedSci原创
近日,一项来自美国的发表于JAMA杂志上的研究"Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure"证实,与非脓毒症死亡患者相比,重症监护室(ICU)住院脓毒症死亡患者存在免疫抑制生化、流式细胞学和免疫组化表现,免疫强化治疗对其可有效。 该研究共纳入40例因活动性严重脓毒症而死于ICU内的患者,
近日,一项来自美国的发表于JAMA杂志上的研究"Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure"证实,与非脓毒症死亡患者相比,重症监护室(ICU)住院脓毒症死亡患者存在免疫抑制生化、流式细胞学和免疫组化表现,免疫强化治疗对其可有效。
该研究共纳入40例因活动性严重脓毒症而死于ICU内的患者,并在受试者死亡后,立即采集其脾脏和肺组织样本以明确患者死亡时的免疫状态特征。脓毒症和49例对照组患者的平均年龄分别为71.7和52.7岁,脓毒症中位持续时间为4天。
结果显示,脓毒症患者的细胞因子分泌总量较对照组减少了10%,与年龄、脓毒症持续时间、激素应用和营养状况无关。
至研究观察第5小时,与对照组相比,脓毒症患者的肿瘤坏死因子(5361 pg/ml对418 pg/ml)、干扰素γ(1374pg/ml对37.5pg/ml)、白介素6(3691pg/ml对365 pg/ml)、白介素10(633pg/ml对58pg/ml)分泌量显著减少,脂多糖刺激细胞因子分泌量亦减少。
流式细胞学分析结果显示,脓毒症患者的脾脏和肺脏两器官内,均有选择性抑制受体和配体表达增加、抑制细胞群扩增。与对照组患者相比,由脓毒症患者肺脏分离出的免疫细胞,在细胞抑制分子表达方面存在独特差异。免疫组化染色显示,脾CD4、CD8和HLA-DR细胞广泛耗竭,肺上皮细胞存在抑制受体配体表达。(生物谷Bioon.com)
Immunosuppression in Patients Who Die of Sepsis and Multiple Organ Failure
Jonathan S. Boomer, PhD; Kathleen To, MD; Kathy C. Chang, PhD; Osamu Takasu, MD; Dale F. Osborne, BS; Andrew H. Walton, MS; Traci L. Bricker, BS; et al.
Context Severe sepsis is typically characterized by initial cytokine-mediated hyperinflammation. Whether this hyperinflammatory phase is followed by immunosuppression is controversial. Animal studies suggest that multiple immune defects occur in sepsis, but data from humans remain conflicting.
Objectives To determine the association of sepsis with changes in host innate and adaptive immunity and to examine potential mechanisms for putative immunosuppression.
Design, Setting, and Participants Rapid postmortem spleen and lung tissue harvest was performed at the bedsides of 40 patients who died in intensive care units (ICUs) of academic medical centers with active severe sepsis to characterize their immune status at the time of death (2009-2011). Control spleens (n = 29) were obtained from patients who were declared brain-dead or had emergent splenectomy due to trauma; control lungs (n = 20) were obtained from transplant donors or from lung cancer resections.
Main Outcome Measures Cytokine secretion assays and immunophenotyping of cell surface receptor-ligand expression profiles were performed to identify potential mechanisms of immune dysfunction. Immunohistochemical staining was performed to evaluate the loss of immune effector cells.
Results The mean ages of patients with sepsis and controls were 71.7 (SD, 15.9) and 52.7 (SD, 15.0) years, respectively. The median number of ICU days for patients with sepsis was 8 (range, 1-195 days), while control patients were in ICUs for 4 or fewer days. The median duration of sepsis was 4 days (range, 1-40 days). Compared with controls, anti-CD3/anti-CD28–stimulated splenocytes from sepsis patients had significant reductions in cytokine secretion at 5 hours: tumor necrosis factor, 5361 (95% CI, 3327-7485) pg/mL vs 418 (95% CI, 98-738) pg/mL; interferon γ, 1374 (95% CI, 550-2197) pg/mL vs 37.5 (95% CI, ?5 to 80) pg/mL; interleukin 6, 3691 (95% CI, 2313-5070) vs 365 (95% CI, 87-642) pg/mL; and interleukin 10, 633 (95% CI, ?269 to 1534) vs 58 (95% CI, ?39 to 156) pg/mL; (P < .001 for all). There were similar reductions in 5-hour lipopolysaccharide-stimulated cytokine secretion. Cytokine secretion in sepsis patients was generally less than 10% that in controls, independent of age, duration of sepsis, corticosteroid use, and nutritional status. Although differences existed between spleen and lung, flow cytometric analysis showed increased expression of selected inhibitory receptors and ligands and expansion of suppressor cell populations in both organs. Unique differences in cellular inhibitory molecule expression existed in immune cells isolated from lungs of sepsis patients vs cancer patients and vs transplant donors. Immunohistochemical staining showed extensive depletion of splenic CD4, CD8, and HLA-DR cells and expression of ligands for inhibitory receptors on lung epithelial cells.
Conclusions Patients who die in the ICU following sepsis compared with patients who die of nonsepsis etiologies have biochemical, flow cytometric, and immunohistochemical findings consistent with immunosuppression. Targeted immune-enhancing therapy may be a valid approach in selected patients with sepsis.
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