Bhatnagar Archana, Wig Jai Dev, Majumdar Siddartha
Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh (Union Territory) 160012, India.
ANZ J Surg. 2003 Jan-Feb;73(1-2):59-64. doi: 10.1046/j.1445-2197.2003.02621.x.
In order to identify the role of mononuclear cells in pancreatitis, the immune picture at the cellular level has been studied. The cytokine production at the individual cell level in response to in vitro stimulation can help in identifying the percentage of specific cell types producing a particular cytokine.
A total of 30 patients with acute pancreatitis (AP; n = 15) and chronic pancreatitis (CP; n = 15) were entered into the study and peripheral blood samples were drawn at the time of admission. A control group of 12 healthy individuals (age and sex matched) were also included in the study. Mononuclear cells from the peripheral blood from all three groups were separated on Ficoll gradient and labelled for surface antigens (i.e. cluster of differentiation (CD)3, CD4, CD8, CD25, CD14 and human leucocyte antigen D receptor (HLA-DR)) using monoclonal antibodies. The CD3+ and CD14+ cells were also stained for intracellular cytokines by specific monoclonal antibodies (i.e. for interferon (IFN)-gamma, interleukin (IL)-2, IL-4 & IL-10 in CD3+ cells and IL-6 and IL-12 in CD14+ cells). These fluorochrome-labelled cells were analysed on the flow cytometer.
The T-cell population is affected in pancreatitis where the CD4+ and CD8+ T-cell numbers are significantly altered. There is a marked reduction in CD4+ T cells in AP and CP. The CD8+ T cells were significantly reduced in AP. The IL-2 receptor is expressed in large numbers in AP and CP patient groups. The T cells from the CP group had a typical IL-2, IL-4 secreting pattern, while AP patients had a high IL-10, IFN-gamma and low IL-2, IL-4 population. The HLA-DR expression on monocytes differed significantly between the two groups, being strikingly reduced in chronic cases and significantly reduced in acute cases. The percentage of IL-6-producing monocytes was significantly higher in patients with AP as well as CP while IL-12 levels were higher in the CP than in the AP group.
T cells in CP are polarized towards the T-helper (Th)1 phenotype while the AP patients had a mixed population. This seems to be a part of immune deviation that is associated with development of CP and IL-12 appears to be instrumental in this process. The monocytes synthesize proinflammatory cytokines, which play an important role in the local and systemic consequences of the disease. In the disease clinical assessment such a study can provide useful information about the involvement of the immuno-inflammatory system.
为了确定单核细胞在胰腺炎中的作用,已对细胞水平的免疫情况进行了研究。体外刺激后单个细胞水平上的细胞因子产生情况有助于确定产生特定细胞因子的特定细胞类型的百分比。
共有30例急性胰腺炎(AP;n = 15)和慢性胰腺炎(CP;n = 15)患者纳入本研究,并在入院时采集外周血样本。研究还纳入了12名健康个体(年龄和性别匹配)作为对照组。通过Ficoll梯度分离所有三组外周血中的单核细胞,并用单克隆抗体标记表面抗原(即分化簇(CD)3、CD4、CD8、CD25、CD14和人类白细胞抗原D受体(HLA-DR))。CD3+和CD14+细胞也用特异性单克隆抗体对细胞内细胞因子进行染色(即CD3+细胞中的干扰素(IFN)-γ、白细胞介素(IL)-2、IL-4和IL-10,以及CD14+细胞中的IL-6和IL-12)。这些荧光染料标记的细胞在流式细胞仪上进行分析。
胰腺炎患者的T细胞群体受到影响,其中CD4+和CD8+T细胞数量发生显著变化。急性胰腺炎和慢性胰腺炎患者的CD4+T细胞明显减少。急性胰腺炎患者的CD8+T细胞显著减少。IL-2受体在急性胰腺炎和慢性胰腺炎患者组中大量表达。慢性胰腺炎组的T细胞具有典型的IL-2、IL-4分泌模式,而急性胰腺炎患者的IL-10、IFN-γ水平较高,IL-2、IL-4水平较低。两组单核细胞上的HLA-DR表达存在显著差异,慢性病例中显著降低,急性病例中也明显降低。急性胰腺炎和慢性胰腺炎患者中产生IL-6的单核细胞百分比显著更高,而慢性胰腺炎组的IL-12水平高于急性胰腺炎组。
慢性胰腺炎患者的T细胞向辅助性T(Th)1表型极化,而急性胰腺炎患者的T细胞群体则较为混合。这似乎是免疫偏离的一部分,与慢性胰腺炎的发展相关,IL-12似乎在这一过程中起作用。单核细胞合成促炎细胞因子,在该疾病的局部和全身影响中起重要作用。在疾病的临床评估中,这样的研究可以提供有关免疫炎症系统参与情况的有用信息。