Expression and clinical significance of NLRP3 and TLR4 in peripheral blood of children with acute wheezing caused by human rhinovirus

doi:10.3877/cma.j.issn.1673-5250.2024.04.011

Objective

To evaluate the expression and clinical significance of NOD-like receptor protein 3（NLRP3）and Toll-like receptor 4（TLR4）in the peripheral blood of children with acute wheezing caused by human rhinovirus（HRV）infection.

Methods

From September 2023 to March 2024，a total of 126 children aged 3-8 who were admitted to Department of Emergency，Qingdao Women and Children's Hospital for the first time with acute wheezing due to HRV infection were selected into this study.According to the severity of the disease，they were divided into mild and moderate group （n=80）and severe group （n=46）.The age，weight，body mass index （BMI），white blood count （WBC），neutrophil count （NEUT），lymphocyte count（LY），C reaction protein（CRP），interleukin （IL）-6，TLR4 and NLRP3 m RNA levels of the two groups were compared by independent samples t test.Chi-square test was used to compare the sex composition ratio，percentage of eczema history and parental allergy history between the two groups.Pearson correlation was used to analyze the correlation between IL-6，TLR4 and NLRP3 m RNA and the severity of acute wheezing attack in children.This study follows the ethical principles and was approved by the Hospital Ethics Committee （Approval No.QFELL-KY-2020-23）.

Results

①There were no statistically significant differences in the gender composition ratio，age，weight，BMI，and the percentage of eczema history and parental allergy history between two groups （P ＞0.05）.②The levels of IL-6，TLR4 and NLRP3 m RNA in the mild to moderate group were lower than those in the severe group （P＜0.05）.③The severity of wheezing in patients with acute wheezing caused by HRV was positively correlated with the levels of IL-6，TLR4 and NLRP3 m RNA （r=0.772，0.792，0.897，P＜0.001）.④There was a positive linear correlation between TLR4 and NLRP3 mRNA （r=0.820，P ＜0.001）.

Conclusions

NLRP3 and TLR4 in peripheral blood of children with acute wheezing caused by HRV infection are closely related to the severity of wheezing.NLRP3 may mediate airway hyperresponsiveness in patients with HRV infection by i nducing IL-6 secretion and up-regulating TLR4 expression，and induce acute wheezing attack.

Key words: Human rhinovirus, Wheezing, NOD-like receptor protein 3, Toll-like receptor 4, Child

表1 2组因HRV 感染致首次喘息急性发作患儿一般临床资料比较

组别	例数	性别［例数（%）］		年龄（岁， $\overset{ˉ}{x}$ ±s）	体重（kg， $\overset{ˉ}{x}$ ±s）	BMI（kg/m²， $\overset{ˉ}{x}$ ±s）	湿疹史［例数（%）］	父母变态反应史［例数（%）］
组别	例数	男	女	年龄（岁， $\overset{ˉ}{x}$ ±s）	体重（kg， $\overset{ˉ}{x}$ ±s）	BMI（kg/m²， $\overset{ˉ}{x}$ ±s）	湿疹史［例数（%）］	父母变态反应史［例数（%）］
轻、中度组	80	36（45.0）	44（55.0）	5.1±1.4	16.5±1.9	13.6±1.8	17（21.3）	8（10.0）
重度组	46	22（47.8）	24（52.2）	4.7±0.9	15.6±1.7	14.1±2.6	13（28.3）	5（10.9）
统计量		χ²=0.09		t=1.91	t=-0.07	t=-1.33	t=0.45	χ²=0.17
P值		0.759		0.069	0.948	0.187	0.501	0.678

表1 2组因HRV 感染致首次喘息急性发作患儿一般临床资料比较

组别	例数	性别［例数（%）］		年龄（岁， $\overset{ˉ}{x}$ ±s）	体重（kg， $\overset{ˉ}{x}$ ±s）	BMI（kg/m²， $\overset{ˉ}{x}$ ±s）	湿疹史［例数（%）］	父母变态反应史［例数（%）］
组别	例数	男	女	年龄（岁， $\overset{ˉ}{x}$ ±s）	体重（kg， $\overset{ˉ}{x}$ ±s）	BMI（kg/m²， $\overset{ˉ}{x}$ ±s）	湿疹史［例数（%）］	父母变态反应史［例数（%）］
轻、中度组	80	36（45.0）	44（55.0）	5.1±1.4	16.5±1.9	13.6±1.8	17（21.3）	8（10.0）
重度组	46	22（47.8）	24（52.2）	4.7±0.9	15.6±1.7	14.1±2.6	13（28.3）	5（10.9）
统计量		χ²=0.09		t=1.91	t=-0.07	t=-1.33	t=0.45	χ²=0.17
P值		0.759		0.069	0.948	0.187	0.501	0.678

表2 2组因HRV 感染致首次喘息急性发作患儿实验室检查结果比较（±s）

组别	例数	WBC（×10⁹/L）	NEUT（×10⁹/L）	LY（×10⁹/L）	CRP（mg/L）	IL-6（pg/mL）	TLR4（ng/L）	NLRP3 mRNA
轻、中度组	80	8.2±2.5	5.0±1.6	3.2±1.9	7.3±3.7	166.4±18.4	53.8±4.7	0.4±0.1
重度组	46	7.6±1.6	4.6±1.7	2.9±1.4	6.5±2.8	224.8±22.4	71.6±5.3	1.7±10.3
t值		1.53	1.22	1.07	1.18	-12.85	-16.18	-23.85
P值		0.129	0.225	0.289	0.242	＜0.001	＜0.001	＜0.001

表2 2组因HRV 感染致首次喘息急性发作患儿实验室检查结果比较（±s）

组别	例数	WBC（×10⁹/L）	NEUT（×10⁹/L）	LY（×10⁹/L）	CRP（mg/L）	IL-6（pg/mL）	TLR4（ng/L）	NLRP3 mRNA
轻、中度组	80	8.2±2.5	5.0±1.6	3.2±1.9	7.3±3.7	166.4±18.4	53.8±4.7	0.4±0.1
重度组	46	7.6±1.6	4.6±1.7	2.9±1.4	6.5±2.8	224.8±22.4	71.6±5.3	1.7±10.3
t值		1.53	1.22	1.07	1.18	-12.85	-16.18	-23.85
P值		0.129	0.225	0.289	0.242	＜0.001	＜0.001	＜0.001

图1 NLRP3 m RNA 及IL-6、TLR4与儿童喘息严重程度相关性的热力图注：IL-6 为白细胞介素6，TLR4 为Toll样受体4，NLRP3 为NOD样受体蛋白3。Severity为疾病严重程度，value表示相关性强度

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