Buchwald U K, Geerdes-Fenge H F, Vöckler J, Ziege S, Lode H
Department of Chest and Infectious Diseases, City Hospital Heckeshorn/Zehlendorf, Zum Heckeshorn 33, D-14109 Berlin, Germany.
Eur J Med Res. 1999 Mar 26;4(3):85-94.
Interleukin-10 (IL-10) has potent anti-inflammatory and immunosuppressive properties. The potential therapeutic benefit may be compromised by the down-regulation of the non-specific immune system and an increased risk of infection. We studied the effects of IL-10 on important functions of native and granulocyte-macrophage colony-stimulating factor (GM-CSF) activated neutrophils and monocytes, namely phagocytosis and membrane expression of the beta superset2-integrins and of the intercellular adhesion molecule-1 (ICAM-1). In order to simulate the in vivo situation closely, we used whole blood flowcytometric assays. The effects of IL-10 (0.05, 1, 10, 100 ng/ml) were compared to those of prednisolone (10 superset-8-10 superset-5 Mol/l), an approved immunosuppressive drug which is known to impair phagocyte function. - Incubation with IL-10 for three hours significantly attenuated the ability of neutrophils to phagocytose E.coli, particularly in lower concentrations. On the other hand, high IL-10 concentrations (10, 100 ng/ml) slightly augmented monocyte phagocytosis. Similarly, expression of the beta subset2-integrins and of ICAM-1 on monocytes was markedly enhanced with IL-10 concentrations in the range from 1 to 100 ng/ml and IL-10 showed strong synergistic effects with GM-CSF in the enhancement of monocyte receptor expression. Neutrophil adhesion molecule expression was not affected. Prednisolone suppressed the phagocytosis of both cell types in a dose-dependent fashion but hardly altered the receptor numbers. Our study indicates that IL-10 can behave as a de-activator as well as an activator on the non-specific immune system, depending on the cell type and the concentration.
白细胞介素-10(IL-10)具有强大的抗炎和免疫抑制特性。非特异性免疫系统的下调以及感染风险的增加可能会损害其潜在的治疗益处。我们研究了IL-10对天然和粒细胞-巨噬细胞集落刺激因子(GM-CSF)激活的中性粒细胞和单核细胞重要功能的影响,即吞噬作用以及β2整合素和细胞间黏附分子-1(ICAM-1)的膜表达。为了更紧密地模拟体内情况,我们使用了全血流式细胞术检测。将IL-10(0.05、1、10、100 ng/ml)的作用与泼尼松龙(10⁻⁸ - 10⁻⁵ Mol/l)的作用进行比较,泼尼松龙是一种已获批的免疫抑制药物,已知会损害吞噬细胞功能。用IL-10孵育三小时显著减弱了中性粒细胞吞噬大肠杆菌的能力,尤其是在较低浓度时。另一方面,高浓度的IL-10(10、100 ng/ml)略微增强了单核细胞的吞噬作用。同样,IL-10浓度在1至100 ng/ml范围内时,单核细胞上β2整合素和ICAM-1的表达明显增强,并且IL-10在增强单核细胞受体表达方面与GM-CSF表现出强烈的协同作用。中性粒细胞黏附分子的表达未受影响。泼尼松龙以剂量依赖的方式抑制了两种细胞类型的吞噬作用,但几乎未改变受体数量。我们的研究表明,根据细胞类型和浓度,IL-10在非特异性免疫系统上既可以表现为去激活剂,也可以表现为激活剂。