尿胰蛋白酶抑制剂对重症结核病患者的免疫调节作用

doi:10.3877/cma.j.issn.1674-6880.2018.06.003

目的

探究尿胰蛋白酶抑制剂（UTI）对重症结核病患者的免疫调节作用。

方法

选取杭州市红十字会医院2015年1月至2017年11月收治的84例重症结核病患者，采用随机数字表法分为UTI组和对照组，每组各42例。对照组给予常规治疗，UTI组在常规治疗基础上于入住ICU第2天给予UTI 10万单位静脉注射，每8小时1次，连续治疗7 d。比较两组患者的一般资料、急性病生理学和长期健康评价（APACHE）Ⅱ评分和外周血液中白细胞介素2（IL-2）、IL-6、IL-10、IL-12、干扰素γ（INF-γ）、转化生长因子β（TGF-β）、肿瘤坏死因子α（TNF-α）、CD4⁺T淋巴细胞、CD8⁺T淋巴细胞、Tregs细胞及诱导性共刺激分子（ICOS）⁺Tregs细胞表达水平。

结果

治疗后，UTI组及对照组重症结核病患者APACHEⅡ评分[（22.5 ± 2.2）分vs.（25.8 ± 1.5）分，t = 2.025，P = 0.043]、IL-6 [（137 ± 33）ng / L vs.（116 ± 42）ng / L，t = 2.785，P = 0.045]、IL-10 [（29 ± 6）ng / L vs.（26 ± 5）ng / L，t = 2.143，P = 0.039]、IL-12 [（84 ± 26）ng / L vs.（65 ± 22）ng / L，t = 2.009，P = 0.043]、TGF-β [（8.5 ± 2.3）ng / L vs.（9.8 ± 2.8）ng / L，t = 1.613，P = 0.045]、CD8⁺T淋巴细胞[（43 ± 13）% vs.（38 ± 12）%，t = 1.856，P = 0.043]及Tregs细胞[（5.8 ± 1.1）% vs.（5.1 ± 0.9）%，t = 1.645，P = 0.045]比率比较，差异均有统计学意义；而IL-2[（835 ± 188）ng / L vs.（744 ± 324）ng / L，t = 0.656，P = 0.458]、INF-γ [（200 ± 88）ng / L vs.（203 ± 78）ng / L，t = 0.912，P = 0.061]、TNF-α [（854 ± 256）μg / L vs.（808 ± 213）μg / L，t = 0.956，P = 0.785]、CD4⁺T淋巴细胞[（48 ± 8）% vs.（49 ± 14）%，t = 0.756，P = 0.985]及ICOS⁺Tregs细胞[（1.0 ± 0.7）% vs.（1.0 ± 0.9）%，t = 0.956，P = 0.089]比率比较，差异均无统计学意义。

结论

UTI能够调节危重症结核病患者的细胞免疫，减轻重症结核病患者体内炎症因子的释放，从而改善其APACHEⅡ评分及预后。

关键词: 尿胰蛋白酶抑制剂, 结核病, 危重症, 免疫调节

Objective

To explore the immunomodulatory effect of urinary trypsin inhibitor (UTI) on patients with severe tuberculosis.

Methods

Totally 84 patients with severe tuberculosis admitted to Hangzhou Red Cross Hospital from January 2015 to November 2017 were randomly divided into the UTI group and control group, with 42 cases in each group. The control group was given conventional treatment, while the UTI group received intravenous injection of UTI, 100 000 units every 8 hours for 7 days on the second day of admission to ICU based on conventional treatment. The general information, acute physiology and chronic health evaluation (APACHE) Ⅱ score, and expressions of interleukin-2 (IL-2), IL-6, IL-10, IL-12, interferon-gamma (INF-γ), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), CD4⁺T lymphocytes, CD8⁺T lymphocytes, Tregs cells and inducible costimulatory molecule (ICOS)⁺ Tregs cells in peripheral blood were compared between those two groups.

Results

After treatment, the APACHEⅡ score [(22.5 ± 2.2) vs. (25.8 ± 1.5), t = 2.025, P = 0.043], IL-6 [(137 ± 33) ng / L vs. (116 ± 42) ng / L, t = 2.785, P = 0.045)], IL-10 [(29 ± 6) ng / L vs. (26 ± 5) ng / L, t = 2.143, P = 0.039], IL-12 [(84 ± 26) ng / L vs. (65 ± 22) ng / L, t = 2.009, P = 0.043], TGF-β [(8.5 ± 2.3) ng / L vs. (9.8 ± 2.8) ng / L, t = 1.613, P = 0.045], CD8⁺T lymphocytes [(43 ± 13)% vs. (38 ± 12)%, t = 1.856, P = 0.043)] and Tregs cells [(5.8 ± 1.1)% vs. (5.1 ± 0.9)%, t = 1.645, P = 0.045] of patients with severe tuberculosis were significantly different between the UTI group and control group. There were no significant differences of IL-2 [(835 ± 188) ng / L vs. (744 ± 324) ng / L, t = 0.656, P = 0.458], INF-γ [(200 ± 88) ng / L vs. (203 ± 78) ng / L, t = 0.912, P = 0.061], TNF-α [(854 ± 256) μg / L vs. (808 ± 213) μg / L, t = 0.956, P = 0.785], CD4⁺T lymphocytes [(48 ± 8)% vs. (49 ± 14)%, t = 0.756, P = 0.985] and ICOS⁺Tregs cells [(1.0 ± 0.7)% vs. (1.0 ± 0.9)%, t = 0.956, P = 0.089] between these two groups.

Conclusion

UTI can regulate the cellular immunity and reduce the release of inflammatory factors in patients with severe tuberculosis, thereby improving their APACHE Ⅱ score and prognosis.

Key words: Urinary trypsin inhibitor, Tuberculosis, Critical illness, Immunomodulation

表1 两组重症结核病患者IL-2、IL-6、IL-10、IL-12、INF-γ、TGF-β及TNF-α表达水平比较（ ± s）

组别		例数	IL-2(ng/L)	IL-6(ng/L)	IL-10(ng/L)	IL-12(ng/L)	INF-γ(ng/L)	TGF-β(ng/L)	TNF-α(μg/L)
UTI组		?	?	?	?	?	?	?	?
?	治疗前	42	554 ± 155	457 ± 46	22 ± 9	129 ± 46	154 ± 65	13.4 ± 5.6	646 ± 127
?	治疗后	42	835 ± 188	137 ± 33	29 ± 6	84 ± 26	200 ± 88	8.5 ± 2.3	854 ± 256
对照组		?	?	?	?	?	?	?	?
?	治疗前	42	524 ± 124	478 ± 68	22 ± 4	131 ± 52	148 ± 89	12.8 ± 7.5	689 ± 146
?	治疗后	42	744 ± 324	116 ± 42^a	26 ± 5^a	65 ± 22^a	203 ± 78	9.8 ± 2.8^a	808 ± 213

表1 两组重症结核病患者IL-2、IL-6、IL-10、IL-12、INF-γ、TGF-β及TNF-α表达水平比较（ ± s）

组别		例数	IL-2(ng/L)	IL-6(ng/L)	IL-10(ng/L)	IL-12(ng/L)	INF-γ(ng/L)	TGF-β(ng/L)	TNF-α(μg/L)
UTI组		?	?	?	?	?	?	?	?
?	治疗前	42	554 ± 155	457 ± 46	22 ± 9	129 ± 46	154 ± 65	13.4 ± 5.6	646 ± 127
?	治疗后	42	835 ± 188	137 ± 33	29 ± 6	84 ± 26	200 ± 88	8.5 ± 2.3	854 ± 256
对照组		?	?	?	?	?	?	?	?
?	治疗前	42	524 ± 124	478 ± 68	22 ± 4	131 ± 52	148 ± 89	12.8 ± 7.5	689 ± 146
?	治疗后	42	744 ± 324	116 ± 42^a	26 ± 5^a	65 ± 22^a	203 ± 78	9.8 ± 2.8^a	808 ± 213

表2 两组重症结核病患者外周血液CD4⁺T淋巴细胞、CD8⁺T淋巴细胞、Tregs细胞及ICOS⁺Tregs细胞比率变化（%， ± s）

组别		例数	CD4⁺T淋巴细胞	CD8⁺T淋巴细胞	Tregs细胞	ICOS⁺Tregs细胞
UTI组		?	?	?	?	?
?	治疗前	42	44 ± 10	35 ± 12	4.1 ± 1.2	0.9 ± 0.3
?	治疗后	42	48 ± 8	43 ± 13	5.8 ± 1.1	1.0 ± 0.7
对照组		?	?	?	?	?
?	治疗前	42	46 ± 12	35 ± 8	4.3 ± 1.5	0.9 ± 0.5
?	治疗后	42	49 ± 14	38 ± 12^a	5.1 ± 0.9^a	1.0 ± 0.9

表2 两组重症结核病患者外周血液CD4⁺T淋巴细胞、CD8⁺T淋巴细胞、Tregs细胞及ICOS⁺Tregs细胞比率变化（%， ± s）

组别		例数	CD4⁺T淋巴细胞	CD8⁺T淋巴细胞	Tregs细胞	ICOS⁺Tregs细胞
UTI组		?	?	?	?	?
?	治疗前	42	44 ± 10	35 ± 12	4.1 ± 1.2	0.9 ± 0.3
?	治疗后	42	48 ± 8	43 ± 13	5.8 ± 1.1	1.0 ± 0.7
对照组		?	?	?	?	?
?	治疗前	42	46 ± 12	35 ± 8	4.3 ± 1.5	0.9 ± 0.5
?	治疗后	42	49 ± 14	38 ± 12^a	5.1 ± 0.9^a	1.0 ± 0.9

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Immunomodulatory effect of urinary trypsin inhibitor on patients with severe tuberculosis

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