Pro- and anti-inflammatory cytokines during acute severe pancreatitis: An early and sustained response, although unpredictable of death
Pro- and anti-inflammatory cytokines during acute severe pancreatitis: An early and sustained response, although unpredictable of death
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DOI：
10.1097/00003246-199904000-00029
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发表时间：
1999-04-01
影响因子：
8.8
通讯作者：
Galanaud, P
中科院分区：
文献类型：
--
作者：
Brivet, FG;Emilie, D;Galanaud, P
目的：明确急性重症胰腺炎患者的促炎和抗炎细胞因子反应，并评价其对医院死亡率的预测价值。设计：前瞻性多中心研究。设置：9个多学科重症监护病房(ICU)。患者：50例确诊为急性胰腺炎的患者，在14个月期间住ICU。干预：无、测量和主要结果：在入院时和ICU期间测定血浆肿瘤坏死因子(TNF)-α-IL-1β、IL-6、IL-10、IL-1受体拮抗剂(IL-1ra)的浓度。根据年龄、性别、既往健康状况、既往存在的器官功能障碍和急性胰腺炎的类型对患者群体进行分析。测定入选时和ICU期间的生理指标，计算新的简化急性生理学评分II、急性生理学和慢性健康状况评分II(APACHE II)以及器官系统衰竭的个数，用单因素分析和逐步Logistic回归分析确定预后因素。纳入50例患者，其中入院时34例，症状前病史小于或等于43小时者占78%。11名患者(22%)在住院期间死亡。在纳入时，50名患者中有46名患者血清IL-6水平升高(1512+/-635pg/m L；正常值10pg/m l)，36%的患者肿瘤坏死因子-α浓度升高，所有患者均有抗炎反应(IL-10，92+/-15pg/m l[正常值<；10pg/m L]；和/或IL-1ra，7271+/-2530pg/m l[正常值<；200 mg/mL)，在随访期内，至少75%的人群中促炎和抗炎细胞因子水平仍然升高，包涵体蛋白(IL-6)与第1天的抗炎细胞因子浓度(IL-10、IL-1ra；p<；在单因素分析中，住院死亡率与6个因素(年龄、肝硬变、入院至ICU的延迟时间、病情严重程度、IL-10和IL-6水平)有关，但只有严重程度评分指数能预测死亡。结论：急性重症胰腺炎期间，促炎和抗炎细胞因子反应发生较早，并在体循环中持续数天，尽管与患者的严重程度和预后相关，但细胞因子血浆浓度不能准确预测单个患者的死亡。如果得到证实，在选择容易从旨在改变免疫炎症反应的新疗法中受益的患者时，应该考虑这些结果。
Objectives: To define the pro and anti-inflammatory cytokine response during acute severe pancreatitis and to evaluate its predictive value on hospital mortality,Design: Prospective, multicenter study.Setting: Nine multidisciplinary intensive care units (ICUs).Patients: Fifty patients with a diagnosis of acute pancreatitis who were admitted to the ICUs during a 14-month period were prospectively enrolled.Interventions: None,Measurements and Main Results: Plasma concentrations of tumor necrosis factor (TNF)-alpha interleukin (IL)-1 beta, IL-6, IL-10, IL-1 receptor antagonist (IL-1ra) were determined at the inclusion and during the ICU stay at Days 1, 3, 8, and 15, The patient population was analyzed by age, gender, previous health status, preexisting organ dysfunction, and type of acute pancreatitis. Physiologic variables were measured at inclusion and during ICU stay to calculate the new Simplified Acute Physiology Score II, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and the number of organ system failures, Prognostic factors were deter mined by univariate methods and stepwise logistic regression analysis, Fifty patients were included, among whom 34 at the time of the ICU admission, Preinclusion symptom history was less than or equal to 43 hrs in 78% of the patients. Eleven patients (22%) died during their hospital stay. At inclusion, 46 of 50 patients had elevated IL-6 serum levels (1512 +/- 635 pg/mL; normal value < 10 pg/mL), 36% of the patients had raised TNF-alpha concentrations, and all patients had an anti inflammatory response (IL 10, 92 +/- 15 pg/mL [normal value < 10 pg/mL]; and/or IL-1ra, 7271 +/- 2530 pg/mL [normal value < 200 mg/mL]), During the follow-up period, pro- and anti-inflammatory cytokines remained elevated in at least 75% of the population, Positive correlations were found between inclusion pro (IL-6) and anti inflammatory cytokine concentrations at Day 1 (IL-10, IL-1ra; p < .0001) and between cytokines levels and the Simplified Acute Physiology Score II. While hospital mortality was linked to six factors in univariate analysis (age, cirrhosis, delay between hospitalization and ICU admission, severity of illness, and IL-10 and IL-6 plasma levels) when using stepwise logistic regression, only severity scoring indexes were predictive of death.Conclusions: During acute severe pancreatitis, the pro- and anti-inflammatory cytokine response occurred early and persisted in the systemic circulation for several days, Although associated with the patient's severity at inclusion and outcome, cytokine plasma concentrations were unable to predict death accurately in individual patients. If confirmed, these results should be taken into consideration when selecting patients who are apt to benefit from new therapies aimed at modifying the immune inflammatory response.