Department of Hepatogastroenterology, Linkou Medical Center, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Hum Immunol. 2011 Jan;72(1):18-23. doi: 10.1016/j.humimm.2010.10.002. Epub 2010 Oct 29.
Immunoparalysis, defined as downregulation of human leukocyte antigen-DR (HLA-DR) expression on monocytes, is strongly associated with septic complications of acute pancreatitis. However, the possible causes of this immunoparalysis have been largely unknown. A prospective case control study was performed in 54 patients with acute pancreatitis and 24 normal volunteers. HLA-DR expression on monocytes and serum cytokine levels were measured. In addition, monocytes from normal volunteers treated with tumor necrosis factor (TNF)-α in vitro were evaluated for HLA-DR expression and cytokine release. HLA-DR expression was significantly lower in patients with severe pancreatitis than in those with mild acute pancreatitis and healthy volunteers (42.28% ± 11.49% vs. 86.85% ± 14.56% vs. 93.92% ± 7.40%, p < 0.0001). Pearson correlation analysis showed that serum TNF-α and serum interleukin-10 levels were both correlated with HLA-DR expression. In addition, exogenous TNF-α could enhance IL-10 secretion from normal monocytes in a dose-response manner. In addition, TNF-α could downregulate the HLA-DR expression on monocytes even in the presence of anti-IL-10 antibodies. Therefore, both TNF-α and IL-10 contributed to the development of immunoparalysis in patients with acute pancreatitis.
免疫麻痹定义为单核细胞人白细胞抗原-DR（HLA-DR）表达下调，与急性胰腺炎的感染性并发症密切相关。然而，这种免疫麻痹的可能原因在很大程度上尚不清楚。本研究对 54 例急性胰腺炎患者和 24 名正常志愿者进行了前瞻性病例对照研究。测定了单核细胞 HLA-DR 表达和血清细胞因子水平。此外，还检测了体外用肿瘤坏死因子（TNF）-α处理的正常志愿者单核细胞的 HLA-DR 表达和细胞因子释放。重症胰腺炎患者单核细胞 HLA-DR 表达明显低于轻症急性胰腺炎患者和健康志愿者（42.28%±11.49%比 86.85%±14.56%比 93.92%±7.40%，p<0.0001）。Pearson 相关分析显示，血清 TNF-α和血清白细胞介素-10 水平均与 HLA-DR 表达相关。此外，外源性 TNF-α可呈剂量依赖性增强正常单核细胞中 IL-10 的分泌。此外，TNF-α甚至在存在抗 IL-10 抗体的情况下也可以下调单核细胞上的 HLA-DR 表达。因此，TNF-α和 IL-10 均有助于急性胰腺炎患者免疫麻痹的发生。
