The Role of Immune Regulatory Mechanisms in the Pathogenesis of Periapical Periodontitis

慢性根尖周炎是一种慢性破坏性疾病，其特征是根管系统感染的细菌与宿主免疫细胞相互作用。局部宿主反应导致根尖周病变中广泛的促炎和抗炎细胞因子和介质的释放。我们定量检测了根尖周液中IL-1β和IL-1ra的水平，表明IL-1ra介导的拮抗作用阻断了局部产生的IL-1活性。IL-1ra/IL-1β比值降低导致根尖周炎性反应增强。我们的定量分析还显示，有症状的根尖周围病变的根尖周围渗出液中IL-8的产生增加。IL-8水平与NO水平呈显著正相关。采用半定量RT-PCR方法检测根尖周组织中促炎症和抗炎细胞因子及生长因子的表达。结果显示，COX…在所有被测试的样本中都存在更多的-2和IL-8信息，这表明在根尖周围病变中促炎介质的产生上调。而抗炎细胞因子、IL-10和转化生长因子-β-1m RNA在大多数标本中均有表达。我们还显示在大多数测试样本中存在IGF-1和EGF消息。体外研究还发现，人单核细胞长期暴露于牙龈卟啉单胞菌脂多糖可诱导其耐受，导致细胞功能的选择性上调或下调。我们的数据还表明，IL-10以自分泌方式介导了牙龈假单胞菌对内毒素耐受单核细胞中IL-6的下调。这些结果提示，促炎和抗炎的细胞因子和介质可能参与了慢性炎症性根尖周炎的调节。总之，对这些影响根尖病变的细胞因子和介质的确切作用的剖析可能会为开发新的诊断方法和治疗药物提供机会。较少

Chronic periapical periodontitis is a chronic destructive disease characterized by an interaction of bacteria infected in the root canal system and the host immune cells. The local host response results in the release of wide array of the pro-and anti-inflammatory cytokines and mediators in the periapical lesion. We quantified the levels of IL-1β and IL-1ra in periapical exudates, and indicated that IL-1ra-mediated antagonism occurred to block locally produced IL-1 activity. Decreased IL-1ra : IL-1β ratio resulted in an acute and higher inflammatory activity in periapical lesion. Our quantitative analysis also revealed increased IL-8 production in the periapical exudate from symptomatic periapical lesion. A significantly positive correlation was found between IL-8 and nitric oxide levels. Semi-quantitative RT-PCR analysis was performed to determine the expression of pro- and anti-inflammatory cytokine and growth factor messages in the periapical tissue specimen. Results showed that COX … More -2 and IL-8 messages were present in all samples tested, and suggested up-regulated production of pro-inflammatory mediators in periapical lesions. On the other hand, anti-inflammatory cytokines, IL-10 and TGF-β1 mRNA was detected in most samples. We also showed the presence of IGF-1 and EGF messages in the majority of test specimens. In vitro studies also revealed that the chronic exposure of human monocytes to Porphyromonas gingivalis LPS resulted in the induction of LPS tolerance that resulted in the selective up-or down-regulation of cell functions. Our data also suggested that IL-10 mediate IL-6 down-regulation in P. gingivalis LPS-tolerant monocytes in an autocrine manner. These results suggest the potential involvement of both the pro-and anti-inflammatory cytokines and mediators in the regulation of chronic inflammatory disease periapical periodontitis. In conclusion, dissection of the precise role of these cytokines and mediators that have an impact on perapical pathogenesis may provide opportunities for the development of new diagnostic procedures and therapeutic agents. Less