炎症指标和细胞因子联合检测在慢性牙周炎中的应用

doi:10.19723/j.issn.1671-167X.2025.04.023

摘要/Abstract

摘要：

目的: 分析慢性牙周炎患者血清和唾液中炎症指标和细胞因子水平，探索单一指标或多指标联合检测在慢性牙周炎临床诊疗中的价值。方法: 对北京大学口腔医院牙周科收治的42例慢性牙周炎患者和38例牙周健康者的血清和唾液标本进行炎症指标和细胞因子检测，比较其在两组间的差异。根据临床牙周参数对慢性牙周炎患者进行临床分期，分析炎症指标和细胞因子水平与慢性牙周炎严重程度的相关性。本研究涉及3项炎症指标[C反应蛋白(C-reactive protein，CRP)、血清淀粉样蛋白A(serum amyloid A，SAA)和降钙素原(procalcitonin，PCT)]和12项细胞因子[白细胞介素(interleukin，IL)-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12P70、IL-17、干扰素(interfe-ron，IFN)-α、IFN-γ和肿瘤坏死因子α(tumor necrosis factor α，TNF-α)]。采用Spearman相关分析评估炎症指标、细胞因子水平与慢性牙周炎严重程度的关系，采用Mann-Whitney U检验识别出组间有差异的指标，通过二元Logistic回归筛选出最优指标，绘制受试者工作特征(receiver operating characteristic，ROC)曲线并计算曲线下面积(area under curve，AUC)，以评估诊断效能。结果: 血清CRP、SAA、IL-8和唾液IL-1β、IL-6、IL-8、IL-12P70、IL-17、TNF-α与慢性牙周炎的严重程度呈显著正相关。与牙周健康组比较，慢性牙周炎组血清中CRP、SAA、IL-2、IL-5、IL-8、IL-12P70、IL-17和IFN-α显著升高(均P < 0.05)，其中SAA、IL-2、IL-8、IL-12P70、IL-17、IFN-α以及组合1(IL-2+IL-8)、组合2(CRP+SAA+IL-12P70)的AUC值>0.7，尤其是组合2的AUC值(0.998)最高，具有高敏感性(97.6%)和特异性(97.4%)，单一指标中IL-8的AUC值(0.992)最高。慢性牙周炎组唾液中IL-1β、IL-6、IL-8、IL-12P70水平显著高于牙周健康组，IL-4水平显著低于牙周健康组(均P < 0.05)，其中IL-6、IL-8和组合3(IL-4+IL-6+IL-8)的AUC值>0.7，尤其是组合3的AUC值(0.852)最高。比较单一指标和多指标联合的诊断效能，组合2、组合1和血清IL-8的AUC值居前3位，多指标联合检测表现出比单一指标更高的AUC。结论: 血清IL-8、CRP、SAA及唾液IL-1β、IL-6、IL-8等指标水平对于慢性牙周炎的临床诊疗可能有帮助，其中，血清IL-8和多指标联合检测可能作为识别慢性牙周炎的辅助诊断指标。

关键词: 慢性牙周炎, 炎症指标, 细胞因子, 血清, 唾液

Abstract:

Objective: To analyze the inflammatory indexes and cytokines levels in serum and saliva of patients with chronic periodontitis (CP), and to explore the value of single index or multiple indexes combined detection in the clinical diagnosis and treatment of CP. Methods: The serum and saliva specimens of 42 CP patients and 38 periodontal healthy people admitted to the Department of Periodontology in Peking University Hospital of Stomatology were detected by inflammatory indexes and cytokines. According to clinical periodontal parameters, CP patients were performed by clinical staging, and the correlation between inflammatory indexes and cytokines levels and the severity of CP was analyzed. To evaluate the levels of inflammatory indexes and cytokines in serum and saliva samples in the periodontal health group and CP group. Three inflammatory indexes were involved in this study: C-reactive protein (CRP), serum amyloid A (SAA), procalcitonin (PCT); and 12 cytokines: Interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17, interferon (IFN)-α, IFN-γ, and tumor necrosis factor α (TNF-α). The Spearman correlation statistical method was used to analyze the correlation between the levels of inflammatory indexes and cytokines and the severity of chronic periodontitis. Mann-Whitney U test was used to identify the indicators with differences between the groups, the optimal indicators were identified through binary Logistic regression analysis with stepwise selection, and the area under the curve (AUC) of receiver operating characteristic (ROC) was used to evaluate the diagnostic efficiency. Results: By testing the levels of inflammatory markers and cytokines in patients with chronic periodontitis with dif-ferent clinical stages, it was found that CRP, SAA, IL-8 in serum and IL-1β, IL-6, IL-8, IL-12P70, IL-17, TNF-α in saliva were significantly positively correlated with the severity of chronic periodontitis. Compared with the periodontal healthy group, the serum levels of CRP, SAA, IL-2, IL-5, IL-8, IL-12P70, IL-17 and IFN-α in the CP group were significantly increased (All P < 0.05). The AUC of SAA, IL-2, IL-8, IL-12P70, IL-17, IFN-α, combination 1 (IL-2+IL-8) and combination 2 (CRP+SAA+IL-12P70) were >0.7, and the AUC of combination 2 (0.998) was the highest, with high sensitivity (97.6%) and specificity (97.4%). The levels of IL-1β, IL-6, IL-8 and IL-12P70 in the saliva of the CP group were significantly higher than those in the periodontal healthy group, while the levels of IL-4 in the saliva were significantly lower than those in the periodontal healthy group (All P < 0.05). The AUC of IL-6, IL-8 and combination 3 (IL-4+IL-6+IL-8) were >0.7, and the AUC of combination 3 (0.852) was the highest. In the comparative analysis of diagnostic efficacy between single index and multi-index combined, combination 2, combination 1, and serum IL-8 demonstrated the highest AUC values (ranked top 3), with multi-index combinations exhibiting superior discriminative power over single index. Conclusion: Serum levels of IL-8, CRP, SAA, and salivary levels of IL-1β, IL-6, IL-8, and other indicators may be helpful for the clinical diagnosis and treatment of CP. Serum IL-8 and multiple indicators may be used as an auxiliary diagnostic indice to identify CP.

Key words: Chronic periodontitis, Inflammatory index, Cytokines, Serum, Saliva

中图分类号:

R781.42

包振英, 王雅杰. 炎症指标和细胞因子联合检测在慢性牙周炎中的应用[J]. 北京大学学报（医学版）, 2025, 57(4): 772-778.

Zhenying BAO, Yajie WANG. Application of combined detection of inflammatory indexes and cytokines in chronic periodontitis[J]. Journal of Peking University (Health Sciences), 2025, 57(4): 772-778.

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Items	Healthy controls (n=38)	Chronic periodontitis (n=42)	P
CRP/(mg/L)	0.60 (0.36, 1.62)	1.49 (0.34, 4.78)	0.035
SAA/(mg/L)	1.16 (0.92, 1.69)	2.18 (1.73, 7.18)	< 0.001
PCT/(ng/L)	6.50 (2.75, 13.30)	12.00 (3.00, 21.00)	0.128
IL-1β/(ng/L)	1.04 (0.51, 1.65)	0.50 (0.00, 2.52)	0.285
IL-2/(ng/L)	1.42 (1.05, 2.16)	2.46 (1.71, 3.75)	< 0.001
IL-4/(ng/L)	1.40 (0.75, 2.11)	1.26 (0.67, 1.95)	0.491
IL-5/(ng/L)	1.24 (0.73, 1.74)	1.84 (0.91, 3.93)	0.031
IL-6/(ng/L)	0.72 (0.45, 1.02)	0.24 (0.00, 1.61)	0.095
IL-8/(ng/L)	4.27 (3.31, 5.77)	47.25 (28.59, 76.37)	< 0.001
IL-10/(ng/L)	1.44 (0.72, 1.98)	1.51 (1.33, 1.98)	0.116
IL-12P70/(ng/L)	0.99 (0.78, 1.73)	1.99 (1.45, 2.35)	< 0.001
IL-17/(ng/L)	2.01 (1.36, 2.47)	3.33(2.39, 4.44)	< 0.001
IFN-α/(ng/L)	1.53 (0.92, 2.61)	2.42(1.53, 4.30)	0.002
IFN-γ/(ng/L)	3.69 (2.56, 5.23)	4.16 (2.80, 5.54)	0.784
TNF-α/(ng/L)	2.15 (1.63, 2.59)	1.49 (0.51, 3.17)	0.158

Items	Healthy controls (n=38)	Chronic periodontitis (n=42)	P
IL-1β/(ng/L)	231.53 (124.49, 587.13)	427.51 (171.01, 805.16)	0.025
IL-2/(ng/L)	2.42 (1.65, 3.49)	2.71 (2.19, 3.49)	0.075
IL-4/(ng/L)	1.35 (0.74, 1.86)	0.98 (0.70, 1.22)	0.019
IL-5/(ng/L)	2.42 (0.97, 7.15)	1.87 (1.26, 2.41)	0.336
IL-6/(ng/L)	16.46 (7.85, 31.68)	41.55 (20.84, 55.25)	0.002
IL-8/(ng/L)	343.02 (253.26, 798.46)	932.71 (671.42, 1 467.16)	< 0.001
IL-10/(ng/L)	2.54 (1.65, 4.25)	1.92 (1.51, 3.29)	0.401
IL-12P70/(ng/L)	1.77 (1.38, 2.84)	2.18 (1.87, 2.72)	0.032
IL-17/(ng/L)	2.92 (1.92, 4.73)	2.57 (1.68, 4.75)	0.919
IFN-α/(ng/L)	2.04 (1.53, 2.81)	2.36 (1.25, 3.03)	0.612
IFN-γ/(ng/L)	2.69 (1.62, 5.47)	2.42 (1.44, 5.02)	0.771
TNF-α/(ng/L)	6.95 (4.37, 9.18)	4.74 (1.38, 7.93)	0.066

Index	ρ	P
Serum
CRP	0.450	0.003
SAA	0.368	0.017
IL-8	0.460	0.002
Saliva
IL-1β	0.523	< 0.001
IL-6	0.470	0.002
IL-8	0.732	< 0.001
IL-12P70	0.484	0.001
IL-17	0.439	0.004
TNF-α	0.334	0.030

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