Expression of angiopoietin-2 and inflammatory factors in children with sepsis

doi:10.3877/cma.j.issn.1673-5250.2019.03.014

Objective

To evaluate the relationship between levels of serum angiopoietin (Ang)-2, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and the severity of sepsis in children, and to provide evidence for clinical diagnosis and treatment of children with sepsis.

Methods

A total of 64 cases of children with fever who were treated in Department of Pediatrics, Jinhua Hospital of Zhejiang University and The Children′s Hospital, Zhejiang University School of Medicine were selected as research subjects. Their age ranged from 1 month after birth to 12 years old. They were divided into three groups according to whether they suffered from sepsis or not and the grading standards of sepsis: group A (n=22, children with sepsis), group B [(n=24, children with infection and without systemic inflammatory response syndrome (SIRS)], and group C (n=18, children with severe sepsis). In the same period, another 21 children underwent health examination in Department of Child Healthcare, Jinhua Hospital of Zhejiang University were included into control group. Their age ranged from 3 months after birth to 12 years old. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum Ang-2, IL-6 and TNF-α. The receiver operating characteristic (ROC) curve of level of serum Ang-2 for diagnosing children with severe sepsis among 4 groups were drawn, and the area under the ROC curve (ROC-AUC) was calculated. The optimal critical value of serum Ang-2 level for diagnosing children with severe sepsis was determined according to the principle of maximum Youden index, and its sensitivity and specificity were calculated. Linear correlation analysis was used to analyze the correlation between levels of serum Ang-2 level and serum IL-6 and TNF-α. This study was in line with the requirements of World Medical Association Declaration of Helsinki revised in 2013. The guardians of all children signed the clinical research informed consents.

Results

① There were no significant differences in age, gender composition ratio and other general clinical data among 4 groups (P>0.05). ②There were significant differences among 4 groups in the levels of serum Ang-2, TNF-α and IL-6 (F=261.24, 33.82, 28.00; P all<0.001). Further comparison results showed that the levels of serum Ang-2 and TNF-α in group C were significantly higher than those in group A, group B and control group, and all the differences were statistically significant (level of serum Ang-2: LSD-t=-5.35, -15.98, 25.31, P all<0.001; level of serum TNF-α: LSD-t=-2.24, P=0.030, LSD-t=-4.91, P<0.001, LSD-t=8.59, P<0.001). The level of serum IL-6 in group C was higher than that in group B and control group, respectively, and both the differences were statistically significant (LSD-t=-4.93, 8.50; P all<0.001). ③The results of ROC curve analysis showed that ROC-AUC of serum Ang-2 level in diagnosis of children with severe sepsis was 0.998 (95%CI: 0.946-1.000, P<0.001). According to the principle of maximum Youden index, the optimal critical value of serum Ang-2 level to predict children with severe sepsis was 163.4 ng/L, and its sensitivity and specificity for diagnosis of children with severe sepsis were 100.0% and 98.5%, respectively. ④Among the children in 4 groups, serum Ang-2 level was positively correlated with serum IL-6 and TNF-α levels, respectively (r=0.606, 0.556; P all<0.001).

Conclusions

The level of serum Ang-2 is significantly elevated with the severity of children with sepsis, which can be used to evaluate the severity of children with sepsis. The levels of serum IL-6 and TNF-α are correlated with serum Ang-2 level, which can assist in the diagnosis of children with sepsis.

Key words: Sepsis, Angiopoietin-2, Interleukin-6, Tumor necrosis factor-alpha, ROC curve, Child

表1 4组受试儿一般临床资料比较

组别	例数	年龄(岁，±s)	性别[例数(%)]
组别	例数	年龄(岁，±s)	男	女
A组	22	2.9±0.6	13(59.1)	9(40.9)
B组	24	3.4±0.7	12(50.0)	12(50.0)
C组	18	2.9±0.7	10(55.6)	8(44.4)
对照组	21	3.8±0.8	12(57.1)	9(42.9)
检验值	?	F＝1.29	χ²＝0.43
P值	?	0.283	0.934

表1 4组受试儿一般临床资料比较

组别	例数	年龄(岁，±s)	性别[例数(%)]
组别	例数	年龄(岁，±s)	男	女
A组	22	2.9±0.6	13(59.1)	9(40.9)
B组	24	3.4±0.7	12(50.0)	12(50.0)
C组	18	2.9±0.7	10(55.6)	8(44.4)
对照组	21	3.8±0.8	12(57.1)	9(42.9)
检验值	?	F＝1.29	χ²＝0.43
P值	?	0.283	0.934

表2 4组受试儿血清Ang-2、IL-6、TNF-α水平比较(±s)

组别		例数	血清Ang-2水平(ng/L)	血清IL-6水平(pg/mL)	血清TNF-α水平(pg/mL)
A组		22	154.2±7.6	103.7±7.8	286.4±36.4
B组		24	122.7±12.2	82.6±23.9	246.2±75.7
C组		18	170.5±8.5	106.1±12.3	321.3±32.3
对照组		21	92.5±8.9	64.4±9.6	185.9±29.9
总体比较		?	?	?	?
?	F值	?	261.24	33.82	28.00
?	P值	?	<0.001	<0.001	<0.001
A组vs B组		?	?	?	?
?	LSD-t值	?	11.12	4.67	2.78
?	P值	?	<0.001	<0.001	0.007
A组vs C组		?	?	?	?
?	LSD-t值	?	－5.35	－0.51	－2.24
?	P值	?	<0.001	0.620	0.030
A组vs对照组		?	?	?	?
?	LSD-t值	?	21.07	8.43	6.74
?	P值	?	<0.001	<0.001	<0.001
B组vs C组		?	?	?	?
?	LSD-t值	?	－15.98	－4.93	－4.91
?	P值	?	<0.001	<0.001	<0.001
B组vs对照组		?	?	?	?
?	LSD-t值	?	10.53	3.99	4.11
?	P值	?	<0.001	<0.001	<0.001
C组vs对照组		?	?	?	?
?	LSD-t值	?	25.31	8.50	8.59
?	P值	?	<0.001	<0.001	<0.001

表2 4组受试儿血清Ang-2、IL-6、TNF-α水平比较(±s)

组别		例数	血清Ang-2水平(ng/L)	血清IL-6水平(pg/mL)	血清TNF-α水平(pg/mL)
A组		22	154.2±7.6	103.7±7.8	286.4±36.4
B组		24	122.7±12.2	82.6±23.9	246.2±75.7
C组		18	170.5±8.5	106.1±12.3	321.3±32.3
对照组		21	92.5±8.9	64.4±9.6	185.9±29.9
总体比较		?	?	?	?
?	F值	?	261.24	33.82	28.00
?	P值	?	<0.001	<0.001	<0.001
A组vs B组		?	?	?	?
?	LSD-t值	?	11.12	4.67	2.78
?	P值	?	<0.001	<0.001	0.007
A组vs C组		?	?	?	?
?	LSD-t值	?	－5.35	－0.51	－2.24
?	P值	?	<0.001	0.620	0.030
A组vs对照组		?	?	?	?
?	LSD-t值	?	21.07	8.43	6.74
?	P值	?	<0.001	<0.001	<0.001
B组vs C组		?	?	?	?
?	LSD-t值	?	－15.98	－4.93	－4.91
?	P值	?	<0.001	<0.001	<0.001
B组vs对照组		?	?	?	?
?	LSD-t值	?	10.53	3.99	4.11
?	P值	?	<0.001	<0.001	<0.001
C组vs对照组		?	?	?	?
?	LSD-t值	?	25.31	8.50	8.59
?	P值	?	<0.001	<0.001	<0.001

图1 血清Ang-2水平诊断严重脓毒症患儿的ROC曲线

图2 4组受试儿中，血清Ang-2水平与血清IL-6水平的相关性分析

图3 4组受试儿中，血清Ang-2水平与血清TNF-α水平的相关性分析

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