IL-12和Th亚群细胞在牙周病免疫病理及免疫调节中的作用

Immunopathology and immunomodulatory roles of interleukin-12 in periodontal disease

目的:探讨白细胞介素12(interleukin-12,IL-12)在牙周病免疫病理及免疫调节中的作用。方法:选取2016年1月—2019年1月收治的98例慢性牙周炎患者,按照牙周炎严重程度分为轻度组(30例)、中度组(35例)与重度组(33例),选取同期进行牙周检查的健康者30例作为对照组,观察各组间临床牙周指标[探诊深度(probing depth,PD)、附着丧失(attachment loss,AL)、菌斑指数(plague index,PLI)、出血指数(bleed index,BI)]、外周血中Th细胞表达(Th1、Th2、Th17)、龈沟液及血清中IL-12水平。采用SPSS 20.0软件包对数据进行统计学分析。结果:各组间PD、PLI、BI等指标相比差异有统计学意义(P<0.05);轻、中、重度3组PD、PLI、BI显著高于对照组(P<0.05);轻、中、重度3组AL指标相比差异显著(P<0.05);中、重度组PD、AL、PLI、BI显著高于轻度组(P<0.05),且重度组PD、AL、PLI、BI显著高于中度组(P<0.05);轻、中、重度3组Th1、Th2、Th17显著高于对照组(P<0.05);中、重度组Th1、Th2、Th17显著高于轻度组(P<0.05),且重度组Th1、Th2、Th17显著高于中度组(P<0.05);轻、中、重度龈沟液及血清中IL-12水平显著高于对照组(P<0.05);中、重度组龈沟液及血清中IL-12水平显著高于轻度组(P<0.05),且重度组龈沟液及血清中IL-12水平显著高于中度组(P<0.05);龈沟液及血清中IL-12与PD、AL、PLI、BI、Th1、Th2及Th17等指标呈正相关(P<0.05)。H-E染色中、轻度组淋巴细胞较少,中度组淋巴细胞数目明显增加,重度组淋巴细胞表现为密集状态,同时在细胞间质中出血明显;IL-12蛋白阳性染色结果均在牙龈组织淋巴细胞质中表达,可见明显棕褐色,轻、中、重度3组IL-12蛋白阳性染色在牙龈组织中数量显著高于对照组,且着色随着轻、中、重度炎症变化而加重。结论:IL-12参与牙周病的免疫调节机制,可能是牙周炎发生的关键促炎细胞因子。

PURPOSE:To investigate the immunopathology and immunomodulatory roles of interleukin-12(IL-12)in periodontal disease.METHODS:Ninety-eight patients with chronic periodontitis from January 2016 to January 2019 were enrolled and divided into mild group(30 cases),moderate group(35 cases)and severe group(33 cases)according to the severity of periodontitis;meanwhile,30 healthy subjects who underwent periodontal examination in our hospital were selected as the control group.Clinical periodontal indicators including probing depth(PD),attachment loss(AL),plaque index(PLI),bleeding index(BI),Th cell expression(Th1,Th2,Th17)in peripheral blood,IL-12 levels in gingival crevicular fluid(GCF)and serum were measured.SPSS 20.0 software package was performed to analyze the correlation between IL-12 levels in GCF and serum and Th1,Th2,Th17,PD,AL,PLI,and BI.RESULTS:The differences of PD,PLI and BI among the groups were statistically significant(P<0.05).The levels of PD,PLI and BI in the mild,moderate and severe group were significantly higher than those in the control group(P<0.05).The difference of AL index among mild,moderate and severe group was statistically significant(P<0.05).The PD,AL,PLI,and BI in the moderate and severe group was significantly higher than those in the mild group(P<0.05),and the severe group was significantly higher than the mild group(P<0.05).Th1,Th2 and Th17 were significantly higher in the mild,moderate and severe group than in the control group(P<0.05);the moderate,severe group was significantly higher than the mild group in terms of Th1,Th2 and Th17(P<0.05),and the severe group was significantly higher than the moderate group(P<0.05).The IL-12 levels in GCF and serum of the mild,moderate,and severe groups were significantly higher than those of the control group(P<0.05);IL-12 levels in the the moderate and severe groups were significantly higher than those in the mild group(P<0.05),and the IL-12 were significantly higher in the severe group than in the moderate group(P<0.05);IL-12 was positively correlated with PD,AL,PLI,BI,Th1,Th2 and Th17(P<0.05).H-E staining showed there were fewer lymphocytes in the mild group,more lymphocytes in the moderate group,and dense lymphocytes in the severe group with significant hemorrhage in intercellular mesenchyme.The IL-12 protein positive staining results were expressed in gingival tissue lymphocyte pulp with significant brown observed.The positive staining of IL-12 protein in the gingival tissues in the mild,moderate and severe group was significantly higher than in the control group,and the staining was aggravated with mild,moderate and severe inflammatory changes.CONCLUSIONS:IL-12 is involved in the immunoregulatory mechanism of periodontal disease and may be a key pro-inflammatory cytokine in the development of periodontitis.