皮肌炎患者血清中细胞因子检测及临床意义

目的 探讨皮肌炎（DM）和临床无肌病性皮肌炎（CADM）患者血清细胞因子水平与疾病活动，特别是与皮损和肺间质病变之间的联系。方法 采用酶联免疫吸附测定和流式微珠阵列法检测40例DM/CADM患者血清中白细胞介素（IL）2、IL-4、IL-6、IL-10、IL-17A、IL-18、肿瘤坏死因子、γ干扰素8种细胞因子水平，分析细胞因子与皮损、炎症指标和肺间质病变严重程度的关系。结果 ①DM/CADM患者血清中，IL-6（37.8 ± 45.8 pg/ml）、IL-10（16.1 ± 7.2 pg/ml）和IL-18（492.0 ± 193.1 pg/ml）水平显著高于健康对照组IL-6（12.0 ± 2.7 pg/ml）、IL-10（7.7 ± 1.4 pg/ml）和IL-18（191.1 ± 39.2 pg/ml）水平，均P <0.001。其他5种细胞因子与健康对照组比较，差异无统计学意义；②红细胞沉降率升高患者的血清IL-6水平（49.7 ± 46.8 pg/ml）显著高于红细胞沉降率正常患者（29.1 ± 45.4 pg/ml），P = 0.008；C反应蛋白升高患者的血清IL-6（68.7 ± 59.7 pg/ml）和IL-18（635.1 ± 232.8 pg/ml）水平显著高于C反应蛋白正常患者（IL-6为30.6 ± 40.3 pg/ml，P = 0.013；IL-18为440.2 ± 164.7 pg/ml，P = 0.020）；乳酸脱氢酶升高患者的IL-10（18.4 ± 6.9 pg/ml）、IL-17A（19.6 ± 6.7 pg/ml）和IL-18（529.4 ± 197.2 pg/ml）显著高于乳酸脱氢酶正常患者（IL-10为10.7 ± 4.8 pg/ml，P < 0.001；IL-17A为11.4 ± 6.6 pg/ml，P = 0.001；IL-18为404.9 ± 158.0 pg/ml，P = 0.037）；肌酸激酶升高组与肌酸激酶正常组之间细胞因子水平比较，差异无统计学意义；③具有Gottron丘疹/征的患者血清IL-18水平（513.7 ± 187.2 pg/ml）显著高于无Gottron丘疹/征的患者（297.1 ± 140.4 pg/ml），P < 0.05；④DM/CADM伴肺间质病变的患者血清IL-10（18.0 ± 6.7 pg/ml）和IL-18水平（552.3 ± 192.8 pg/ml）显著高于不伴肺间质病变者（IL-10为11.6 ± 6.5 pg/ml，IL-18为351.4 ± 101.0 pg/ml），P = 0.001。结论 皮肌炎患者血清IL-6、IL-10、IL-18等细胞因子与炎症指标、皮损和肺间质病变显著相关。

Detection of serum cytokines in patients with dermatomyositis and their clinical significance

Chen Mengya, Diao Licheng, Xu Renjie, Li Weiping, Lu Yide, Zheng Jie, Cao Hua Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China （Chen MY, Diao LC, Xu RJ, Li WP, Zheng J, Cao H）; Clinical Laboratory, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China （Lu YD） Corresponding authors: Cao Hua, Email: drcaohua@126.com; Zheng Jie, Email: jie-zheng2001@126.com 【Abstract】 Objective To explore the association of serum cytokine levels with disease activity in patients with dermatomyositis（DM）and clinically amyopathic dermatomyositis（CADM）, especially their association with skin lesions and interstitial lung disease （ILD）. Methods Enzyme-linked immunosorbent assay （ELISA） and cytometric beads array （CBA）were performed to detect the serum levels of interleukin （IL）-2, IL-4, IL-6, IL-10, IL-17A, IL-18, tumor necrosis factor （TNF） and interferon （IFN）-γ in 40 patients with DM or CADM, as well as in 16 health checkup examinees （healthy control group）. Then, the association of serum cytokine levels with skin lesions, inflammatory biomarkers and severity of ILD was analyzed. Results The patients with DM/CADM showed significantly higher serum levels of IL-6 （37.8 ± 45.8 pg/ml）, IL-10 （16.1 ± 7.2 pg/ml） and IL-18 （492.0 ± 193.1 pg/ml） compared with the healthy controls （12.0 ± 2.7 pg/ml, 7.7 ± 1.4 pg/ml, 191.1 ± 39.2 pg/ml, respectively, all P < 0.001）, and there were no significant differences in the serum levels of the other 5 cytokines between the above 2 groups. The serum level of IL-6 was significantly higher in patients with elevated erythrocyte sedimentation rate （ESR） than in those with normal ESR （49.7 ± 46.8 pg/ml vs. 29.1 ± 45.4 pg/ml, P = 0.008）. The patients with raised C-reactive protein （CRP） levels showed significantly higher serum levels of IL-6 （68.7 ± 59.7 pg/ml） and IL-18 （635.1 ± 232.8 pg/ml） compared with those with normal CRP levels （IL-6: 30.6 ± 40.3 pg/ml, P = 0.013；IL-18: 440.2 ± 164.7 pg/ml, P = 0.020）. Moreover, the patients with elevated levels of lactate dehydrogenase （LDH） showed significantly higher serum levels of IL-10 （18.4 ± 6.9 pg/ml）, IL-17A （19.6 ± 6.7 pg/ml） and IL-18 （529.4 ± 197.2 pg/ml） compared with those with normal LDH levels （IL-10: 10.7 ± 4.8 pg/ml, P < 0.001; IL-17A: 11.4 ± 6.6 pg/ml, P = 0.001; IL-18: 404.9 ± 158.0 pg/ml, P = 0.037）. No significant difference in the cytokine levels was observed between the patients with elevated creatine kinase （CK） levels and those with normal CK levels. The patients with Gottron′s papules/sign showed significantly higher serum levels of IL-18 （513.7 ± 187.2 pg/ml） compared with those without Gottron′s papules/sign （297.1 ± 140.4 pg/ml, P < 0.05）. The serum levels of IL-10 and IL-18 were significantly higher in the patients with DM/CADM complicated by ILD （18.0 ± 6.7 pg/ml, 552.3 ± 192.8 pg/ml, respectively） than in those without ILD （11.6 ± 6.5 pg/ml, 351.4 ± 101.0 pg/ml, respectively, both P = 0.001）. Conclusion Serum levels of IL-6, IL-10 and IL-18 are highly associated with inflammatory biomarkers, skin lesions and ILD in patients with DM/CADM.