Gilkeson G S, Conover J, Halpern M, Pisetsky D S, Feagin A, Klinman D M
Ralph H. Johnson Veterans Affairs Medical Center and the Medical University of South Carolina, Charleston 29425, USA.
J Immunol. 1998 Oct 15;161(8):3890-5.
Microbial DNA has multiple immune effects including the capacity to induce polyclonal B cell activation and cytokine production in normal mice. We recently described the accelerated induction of anti-DNA Abs in NZB/NZW mice immunized with Escherichia coli (EC) dsDNA; paradoxically these mice developed less renal disease than unimmunized mice or mice immunized with calf thymus DNA. We postulated that alterations in cytokine production induced by bacterial DNA may play a key role in renal protection. To determine the effect of bacterial DNA on cytokine production in NZB/NZW mice, we measured the serum cytokine levels, cell culture supernatant cytokine levels, and number of cytokine-producing splenocytes in NZB/NZW mice injected with EC DNA, calf thymus DNA, or an immune active oligonucleotide. There was a 10- to 25-fold increase in the number of cells secreting IFN-gamma compared with IL-4 in mice immunized with EC DNA. IL-12-secreting cells were also increased by bacterial DNA immunization. In parallel with the increase in IFN-gamma secreting cells, there was a significant rise in serum IFN-gamma levels in mice receiving EC DNA. These results indicate that EC DNA modulates systemic cytokine levels in NZB/NZW mice, selectively increasing IL-12 and IFN-gamma while decreasing IL-4 production. The cytokine response of NZB/NZW mice to bacterial DNA may be of significance in disease pathogenesis and relevant to the treatment of lupus-like disease.
微生物DNA具有多种免疫效应，包括在正常小鼠中诱导多克隆B细胞活化和细胞因子产生的能力。我们最近描述了用大肠杆菌（EC）双链DNA免疫的NZB/NZW小鼠中抗DNA抗体的加速诱导；矛盾的是，这些小鼠发生的肾脏疾病比未免疫的小鼠或用小牛胸腺DNA免疫的小鼠少。我们推测细菌DNA诱导的细胞因子产生变化可能在肾脏保护中起关键作用。为了确定细菌DNA对NZB/NZW小鼠细胞因子产生的影响，我们测量了注射EC DNA、小牛胸腺DNA或免疫活性寡核苷酸的NZB/NZW小鼠的血清细胞因子水平、细胞培养上清液细胞因子水平以及产生细胞因子的脾细胞数量。与用EC DNA免疫的小鼠中分泌IL-4的细胞相比，分泌IFN-γ的细胞数量增加了10至25倍。细菌DNA免疫也增加了分泌IL-12的细胞。与分泌IFN-γ的细胞增加同时，接受EC DNA的小鼠血清IFN-γ水平显著升高。这些结果表明，EC DNA调节NZB/NZW小鼠的全身细胞因子水平，选择性增加IL-12和IFN-γ，同时减少IL-4的产生。NZB/NZW小鼠对细菌DNA的细胞因子反应可能在疾病发病机制中具有重要意义，并且与狼疮样疾病的治疗相关。
