Tretter T, Aman M J, Bug G, Huber C, Peschel C
IIIrd Department of Medicine, The Johannes Gutenberg University School of Medicine, Mainz, Germany.
J Interferon Cytokine Res. 1998 Feb;18(2):95-102. doi: 10.1089/jir.1998.18.95.
We investigated the influence of interferon-alpha (IFN-alpha) on the synthesis of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) by monocytes and activated T helper cells. IFN-alpha inhibited the production of GM-CSF in unstimulated and lipopolysaccharide (LPS)-activated monocytes to the same extent as was observed in the presence of IL-4. In highly purified CD4+ T cells, which were activated by incubation with immobilized anti-CD3 antibody and anti-CD28, IFN-alpha reduced production of GM-CSF to 47%. In contrast, GM-CSF production in activated T cells was unaffected by exogenously added IL-4. The production of IL-3 by T helper cells was significantly inhibited by IFN-alpha as well. IL-3 production by CD3/CD28-stimulated T helper cells was exclusively enhanced by IL-4. The exogenous addition of IL-4 led to a highly significant increase of IL-3 levels in T cell supernatants to 231% of control cultures (range 137%-605%), whereas other T cell-derived cytokines, such as IFN-gamma and IL-10, failed to influence IL-3 release. The differential role of IL-4 in IL-3 production was confirmed by the addition of anti-IL-4 antibodies to CD3/CD28-stimulated T cells. Neutralizing anti-IL-4 antibody caused a drastic reduction of IL-3 synthesis by activated T cells, whereas GM-CSF production was independent of neutralization of endogenous IL-4. These experiments define IFN-alpha as an inhibitory substance for the production of hematopoietic growth factors by activated immune cells. The influence of IL-4 on cytokine synthesis appears to be cell type specific, thus revealing a differential stimulatory effect on IL-3 production.
我们研究了α干扰素（IFN-α）对单核细胞和活化的辅助性T细胞合成粒细胞-巨噬细胞集落刺激因子（GM-CSF）和白细胞介素-3（IL-3）的影响。IFN-α抑制未刺激的和脂多糖（LPS）激活的单核细胞产生GM-CSF，其抑制程度与在IL-4存在时观察到的相同。在通过与固定化抗CD3抗体和抗CD28孵育而活化的高度纯化的CD4⁺T细胞中，IFN-α将GM-CSF的产生降低至47%。相比之下，活化T细胞中GM-CSF的产生不受外源性添加的IL-4的影响。辅助性T细胞产生IL-3也受到IFN-α的显著抑制。CD3/CD28刺激的辅助性T细胞产生的IL-3仅由IL-4增强。外源性添加IL-4导致T细胞上清液中IL-3水平显著增加至对照培养物的231%（范围为137%-605%），而其他T细胞衍生的细胞因子，如IFN-γ和IL-10，未能影响IL-3的释放。通过向CD3/CD28刺激的T细胞中添加抗IL-4抗体，证实了IL-4在IL-3产生中的不同作用。中和抗IL-4抗体导致活化T细胞合成的IL-3急剧减少，而GM-CSF的产生与内源性IL-4的中和无关。这些实验将IFN-α定义为活化免疫细胞产生造血生长因子的抑制物质。IL-4对细胞因子合成的影响似乎具有细胞类型特异性，从而揭示了对IL-3产生的不同刺激作用。
