Effects of IL-12 on in vivo cytokine gene expression and Ig isotype selection.
Effects of IL-12 on in vivo cytokine gene expression and Ig isotype selection.
复制标题
IL-12 对体内细胞因子基因表达和 Ig 同种型选择的影响。
作者：
S. Morris;K. Madden;Jeffrey J. Adamovicz;W. Gause;Brian R. Hubbard;Maurice K. Gately;F. Finkelman
体内实验研究了小鼠rIL-12对细胞因子基因表达和免疫球蛋白分泌的影响。在未经治疗的小鼠中，IL-12促进了干扰素-γ和IL-10基因的表达和蛋白分泌，降低了基线IL-3和IL-4基因的表达，并升高了血清中的IgG2a浓度。在注射山羊抗鼠IGD抗体(GαM Delta)诱导IL-3、IL-4和IL-10基因表达及血清IgE、IgG1、IgG2a和IgG3浓度升高的小鼠中，同时注射IL-12可增强干扰素-γ和IL-10基因的表达，抑制IL-3和IL-4基因的表达以及血清免疫球蛋白和免疫球蛋白的应答。抗干扰素-伽马单抗中和了大部分，但不是全部，干扰素-伽马由GαM增量和IL-12处理的小鼠产生。抗干扰素-γ单抗增强IL-3和IL-4基因表达，不影响IL-10和干扰素-γ基因表达，升高血清IgG1、IgG2a和IgG3水平，但对血清IgE影响较小。与GαM Delta处理的小鼠相比，IL-12不能抑制GαM epsilon抗体的IgE反应，后者刺激Mige+B细胞分泌IgE。这些观察结果表明：1)IL-12可能通过诱导一种细胞因子(IL-10)的产生来限制其自身的作用，该细胞因子下调IL-12的产生和IL-12诱导的干扰素-γ的产生；2)IL-12抑制至少一种细胞因子-IL-3的产生，而IL-3通常被认为不是严格意义上的Th1或Th2相关的；3)IL-12在更大程度上抑制向IgE分泌的转换，而不是它抑制向其他Ig亚型的转换；以及4)IL-12的体内作用在很大程度上是干扰素-γ依赖的。
The effects of murine rIL-12 on cytokine gene expression and Ig secretion were studied in vivo. In untreated mice IL-12 enhanced IFN-gamma and IL-10 gene expression and protein secretion, reduced base line IL-3 and IL-4 gene expression, and increased serum IgG2a concentration. In mice that had been injected with goat anti-mouse IgD antibody (G alpha M delta) to induce increases in IL-3, IL-4, and IL-10 gene expression and serum IgE, IgG1, IgG2a, and IgG3 concentrations, the simultaneous injection of IL-12 enhanced IFN-gamma and IL-10 gene expression and suppressed IL-3 and IL-4 gene expression and serum IgG and IgE responses. Anti-IFN-gamma mAb neutralized most, but not all, IFN-gamma produced by mice treated with G alpha M delta and IL-12. Anti-IFN-gamma mAb enhanced IL-3 and IL-4 gene expression, did not affect IL-10 or IFN-gamma gene expression, and increased serum IgG1, IgG2a, and IgG3 levels, but had relatively little effect on serum IgE in these mice. In contrast to its effects in G alpha M delta-treated mice, IL-12 failed to inhibit the IgE response to G alpha M epsilon antibody, which stimulates mIgE+ B cells to secrete IgE. These observations demonstrate that: 1) IL-12 may limit its own effects by inducing the production of a cytokine (IL-10) that down-regulates both IL-12 production and IL-12-induced IFN-gamma production; 2) IL-12 inhibits the production of at least one cytokine, IL-3, that is not generally regarded to be strictly Th1- or Th2-associated; 3) IL-12 inhibits switching to IgE secretion to a greater extent than it inhibits switching to other Ig isotypes; and 4) the in vivo effects of IL-12 are, to a large extent, IFN-gamma-dependent.