Littman B H, Dastvan F F, Carlson P L, Sanders K M
Rheumatology Section, McGuire V.A. Medical Center, Richmond, VA 23249.
J Immunol. 1989 Jan 15;142(2):520-5.
IL-4 was originally described on the basis of its ability to co-stimulate the proliferation of resting B cells treated with anti-IgM. Recently, this cytokine has been shown to have other effects on mast cells, T cells, B cells, and macrophages. We studied the ability of IL-4 to regulate the production of C2 by human monocytes and monocytic cell lines and compared this with stimulation of HLA-DR expression, another recently described activity of IL-4. Responses to IL-4 were compared to IFN-gamma, a cytokine with both activities. IL-4 up-regulated C2 production by human monocytes and this effect was not inhibited by neutralizing anti-IFN-gamma antibody. IL-4 also stimulated C2 production by HL-60 cells that had been pre-treated with vitamin D3 to induce monocytic differentiation. IL-4 did not stimulate C2 production by U937 cells. IFN-gamma, in contrast to IL-4, stimulates C2 production by all three cell types. Although IL-4 increased C2 production by HL-60 cells we could not detect C2 mRNA by Northern blotting. However, co-stimulation of these cells with IL-4 and low concentrations of IFN-gamma resulted in an additive effect on C2 production and a greater increase in C2 mRNA than was seen with IFN-gamma alone. As reported by others, IL-4-stimulated HLA-DR expression by monocytes. In contrast to our findings regarding C2 production, stimulation of HLA-DR expression was inhibited by neutralizing anti-IFN-gamma mAb and IL-4 did not stimulate HLA-DR expression by U937 or HL-60 cells. IFN-gamma stimulated HLA-DR expression by all three cell types. These results identify IL-4 as an additional cytokine able to directly stimulate C2 production by human monocytes and by a monocytic cell line whereas IL-4 stimulation of HLA-DR expression by monocytes appears to be IFN-gamma dependent.
白细胞介素-4最初是根据其协同刺激经抗IgM处理的静止B细胞增殖的能力而被描述的。最近，已证明这种细胞因子对肥大细胞、T细胞、B细胞和巨噬细胞有其他作用。我们研究了白细胞介素-4调节人单核细胞和单核细胞系产生C2的能力，并将其与白细胞介素-4最近描述的另一种活性——刺激HLA-DR表达进行了比较。将对白细胞介素-4的反应与具有这两种活性的细胞因子γ干扰素进行了比较。白细胞介素-4上调了人单核细胞的C2产生，并且这种作用不受中和抗γ干扰素抗体的抑制。白细胞介素-4还刺激了经维生素D3预处理以诱导单核细胞分化的HL-60细胞产生C2。白细胞介素-4不刺激U937细胞产生C2。与白细胞介素-4相反，γ干扰素刺激所有这三种细胞类型产生C2。尽管白细胞介素-4增加了HL-60细胞的C2产生，但我们通过Northern印迹法未能检测到C2 mRNA。然而，用白细胞介素-4和低浓度的γ干扰素共同刺激这些细胞，导致对C2产生的相加作用以及C2 mRNA的增加幅度大于单独使用γ干扰素时所见。正如其他人所报道的，白细胞介素-4刺激单核细胞表达HLA-DR。与我们关于C2产生的发现相反，中和抗γ干扰素单克隆抗体抑制了HLA-DR表达的刺激，并且白细胞介素-4不刺激U937或HL-60细胞表达HLA-DR。γ干扰素刺激所有这三种细胞类型表达HLA-DR。这些结果表明白细胞介素-4是另一种能够直接刺激人单核细胞和单核细胞系产生C2的细胞因子，而白细胞介素-4刺激单核细胞表达HLA-DR似乎依赖于γ干扰素。
