急性胰腺炎早期的单核组织相容性白细胞抗原-DR表达
Mononuclear histocompatibility leukocyte antigen-DR expression in the early phase of acute pancreatitis.
作者信息
Yu Wen-Kui, Li Wei-Qin, Li Ning, Li Jie-Shou
机构信息
Department of General Surgery, School of Medince, Nanjing University, Nanjing, PR China.
出版信息
Pancreatology. 2004;4(3-4):233-43. doi: 10.1159/000078748. Epub 2004 May 27.
BACKGROUND
In acute pancreatitis (AP), several studies indicated that the balance between pro- and anti-inflammatory mediators is more important than the levels of proinflammatory response alone. This balance may be reflected by the expression of monocyte histocompatibility leukocyte antigen (HLA)-DR, with a low concentration indicating an excess of anti-inflammatory stimuli and relative immunodeficiency. We investigated the time course of HLA-DR expression in the early phase of AP and the relationship to markers of inflammation, severity of the disease, organ function, septic complications and outcome during AP.
METHODS
The expression of HLA-DR on peripheral monocytes was measured in 74 patients by flow cytometry and serum IL-6 was determined by using an immunochemiluminescence assay obtained 24 h, 48 h, 72 h, 7 days, 10 days and 14 days after admission in parallel with clinical data collection. 25 patients had mild disease (grade 1), 31 had severe disease but recovered without organ failure (grade 2) and 18 had severe disease and developed organ failure (grade 3).
RESULTS
In 49 patients with severe disease, 11 patients suffered from sepsis, and 3 of them died during the hospital stay. During the first 14 days of AP, the percentage of HLA-DR in AP was significantly below the normal range of healthy subjects, it dropped to the lowest level on day 3, but then gradually recovered from the prophase depression. The HLA-DR expression decreased in the order grade 3 < grade 2 < grade 1 (p < 0.001). We also observed a significant inverse correlation between the percentage of HLA-DR+ and AP severity as assessed by APACHE-II scores (r = 0.754, p < 0.001) and MODS score (r = 0.675, p < 0.001). The peak of systemic inflammatory reaction, documented by maximum serum concentration of CRP, coincided with the nadir of HLA-DR suppression. Moreover, IL-6 and CRP serum concentrations were inversely correlated with HLA-DR expression over the entire observation period. Persistent HLA-DR suppression and a second decrease in HLA-DR expression are associated with septic complications and poor outcome.
CONCLUSION
Immune suppression develops early and rapidly in patients with AP, and the degree is parallel with the severity of the disease. Decreases in HLA-DR expression occurred simultaneously with signs of hyperinflammation in the early phase of AP, and persistent HLA-DR suppression and a second decrease in HLA-DR expression are associated with septic complications and poor outcome.
背景
在急性胰腺炎(AP)中,多项研究表明促炎和抗炎介质之间的平衡比单纯的促炎反应水平更为重要。这种平衡可能通过单核细胞组织相容性白细胞抗原(HLA)-DR的表达来反映,低浓度表明抗炎刺激过度和相对免疫缺陷。我们研究了AP早期HLA-DR表达的时间进程以及与炎症标志物、疾病严重程度、器官功能、感染性并发症和AP期间结局的关系。
方法
通过流式细胞术检测74例患者外周血单核细胞上HLA-DR的表达,并在入院后24小时、48小时、72小时、7天、10天和14天使用免疫化学发光法测定血清IL-6,同时收集临床数据。25例患者病情较轻(1级),31例病情严重但未发生器官衰竭而康复(2级),18例病情严重并发生器官衰竭(3级)。
结果
在49例重症患者中,11例发生脓毒症,其中3例在住院期间死亡。在AP的前14天,AP患者中HLA-DR的百分比显著低于健康受试者的正常范围,在第3天降至最低水平,但随后从前期的降低逐渐恢复。HLA-DR表达按3级<2级<1级的顺序降低(p<0.001)。我们还观察到HLA-DR+百分比与通过APACHE-II评分评估的AP严重程度(r=0.754,p<0.001)和多器官功能障碍综合征(MODS)评分(r=0.675,p<0.001)之间存在显著负相关。以CRP血清浓度最大值记录的全身炎症反应高峰与HLA-DR抑制的最低点一致。此外,在整个观察期内,IL-6和CRP血清浓度与HLA-DR表达呈负相关。持续的HLA-DR抑制和HLA-DR表达的再次降低与感染性并发症和不良结局相关。
结论
AP患者早期迅速出现免疫抑制,且程度与疾病严重程度平行。HLA-DR表达的降低与AP早期的炎症亢进迹象同时出现,持续的HLA-DR抑制和HLA-DR表达的再次降低与感染性并发症和不良结局相关。