Changes and effects of multiple immuno-proinflammatory cytokines and anti-inflammatory cytokines in the pathogenesis of patients with hemorrhagic fever and renal syndrome

doi:10.3877/cma.j.issn.1674-1358.2018.04.009

Abstract

Abstract:

Objective

To investigate the changes and effects of proinflammatory cytokines and anti-inflammatory cytokines in acute phase (including febrile phase, hypotension shock phase, oliguria phase) and convalescent patients with hemorrhagic fever and renal syndrome (HFRS).

Methods

Levels of serum tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), transforming growth factor -β1 (TGF-β1), interleukin-6 (IL-6)and interleukin-10 (IL-10) in 30 patients with HFRS from the Fourth Affiliated Hospital of Harbin Medical University and Center Hopital of Heilongjiang Agricultural Reclamation Hongxinglong Administration from April 2016 to June 2017 were detected. And the levels of cystatin C, creatinine (Cr), lactate dehydrogenase (LDH), activated partial thromboplastin time (APTT) of these patients were also dectected. Thirteen healthy volunteers were selected as the control group to detect the above indexes. The results were analyzed by SAS 9.3 International Standard Statistical Programming Software.

Results

The levels of IFN-γ (χ²= 4.273,P= 0.0336), TNF-α (χ²= 16.3562,P <0.0001), IL-6 (χ²= 9.752,P= 0.0018) and IL-10 (χ²= 6.3352,P= 0.0118) of patient with HFRS in acute stage were all significantly higher than those of the control group, all with significant differences (allP< 0.05). TGF-β1 level of patients with HFRS in acute stage was significantly lower than that of the control group, with significant difference (χ² = 7.822,P= 0.0056). The level of TGF-β1 of patient with HFRS in recovery stage was close to or slightly lower than the control group, with no significant difference (χ² = 3.000,P= 0.0833). The levels of Cystatin C, Cr, LDH and APTT of patients at different HFRS stages all showed increase in the acute stage and decrease in the recovery stage, which were consistent with the trend of TNF-α, IFN-γ, IL-6 and IL-10 levels.

Conclusions

At acute stage of HFRS, proinflammatory cytokines such as TNF-α, IFN-γ, IL-6 increased, and anti-inflammatory cytokines such as TGF-β1 secreted by CD4⁺CD25⁺FoxP3 Treg cells (regulatory T cells) decreased. The imbalance of cytokines was an important mechanism that causes the body immunologic pathological injury.

Key words: Proinflammatory cytokine, Anti-inflammatory cytokine, Hemorrhagic fever with renal syndrome

Yu Liu, Liying Zhu, Lei Yu, Lihua Zhong, Jian Fan, Hong Yao. Changes and effects of multiple immuno-proinflammatory cytokines and anti-inflammatory cytokines in the pathogenesis of patients with hemorrhagic fever and renal syndrome[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2018, 12(04): 360-364.

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References 32

[1]	薛江洲,张小凡,孙志坚, 等. 肾综合征出血热肿瘤坏死因子α,干扰素γ,白细胞介素10,转化生长因子β1的变化[J]. 临床荟萃,2007,22(10):692-695.
[2]	Maes P,Clement J,Gavrilovskaya I, et al. Hantaviruses: immunology, treatment, and prevention[J]. Viral Immunol,2004,7(4):481-497.
[3]	Terajima M,Vapalahti O,Van Epps HL, et al. Immune responses to Puumala virus infection and the pathogenesis of nephropathia epidemica[J]. Microbes Infect,2004,6(2):238-245.
[4]	Khaiboullina SF,Martynova EV,Khamidullina ZL, et al. Upregulation of IFN-γ and IL-12 is associated with a milder form of hantavirus hemorrhagic fever with renal syndrome[J]. Eur J Clin Microbiol Infect Dis,2014,33(12):2149-2156.
[5]	Kyriakidis I,Papa A. Serum TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels in hemorrhagic fever with renal syndrome[J]. Virus Res,2013,175(1):91-94.
[6]	Zhu LY,Chi LJ,Wang X, et al. Reduced circulating CD4⁺CD25⁺ cell populations in haemorrhagic fever with renal syndrome[J]. Clin Exp Immunol,2009,156(1):88-96.
[7]	Markotic A. Immunopathogenesis of hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome[J]. Acta Med Croatica,2003,57(5):407-414.
[8]	Raftery MJ,Kraus AA,Ulrich R, et al. Hantavirus infection of dendritic cells[J]. J Viral,2002,76(21):10724-10733.
[9]	李兰娟,任红主编. 传染病学[M]. 8版. 北京: 人民卫生出版社,2013.
[10]	张小凡,孙志坚,薛江洲, 等. 肾综合征出血热血清TNF-α, E-选择素, L-选择素, ICAM-1, TGF-β1的变化及其意义[J]. 南京医科大学学报,2006,26(8):676-679.
[11]	Klingstrom J,Plyusnin A,Vaheri A, et al. Wild-type puumala hantavirus infection induces cytokines, C-Reactive protein, creatinine, and nitric oxide in cynomolgus macaques[J]. J Virol,2002,76(1):444-449.
[12]	江振友,史毓杰,刘小澄, 等. 肾综合征出血热病毒对人外周血单个核细胞产生细胞因子的影响[J]. 免疫学杂志,2005,21(5):374-381.
[13]	Tang K,Zhang C,Zhang Y, et al. Elevated plasma soluble CD14 levels correlate with the monocyte response status during hantaan virus infection in humans[J]. Viral Immunol,2015,28(8):442-447.
[14]	Baigildina AA,Khaiboullina SF,Martynova EV, et al. Inflammatory cytokines kinetics define the severity and phase of nephropathia epidemica[J]. Biomark Med,2015,9(2):99-107.
[15]	周文俊,马韫佳,袁虹萍. 肾综合征出血热患者血清IL-12p70, IFN-γ, IL-4,血浆D-二聚体和血管血友病细胞因子水平及临床意义[J]. 中国实验诊断学,2013,17(10):1830-1833.
[16]	唐利群,周国平. 慢性肾脏病患者干扰素γ的表达及其临床意义[J]. 临床医学研究与实践,2016,1(9):1-2, 6.
[17]	杨帆,吴忠道. 白介素-10产生的相关机制研究进展[J]. 国际医学寄生虫病杂志,2012,39(4):230-235.
[18]	Gorehk L,Constant S,Flavell RA. Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation[J]. J Exp Med,2002,195(11):1499-1505.
[19]	张东军,孙志坚,赵宏, 等. 肾综合征出血热血清细胞因子的变化及其意义[J]. 江苏医药,2004,30(12):901-902.
[20]	Saksida A,Wraber B,Avsic-Zupanc T. Serum levels of inflammatory and regulatory cytokines in patients with hemorrhagic fever with renal syndrome[J]. BMC Infect Dis,2011,23(11):142.
[21]	史国星,曾强,窦剑, 等. CD4⁺CD25⁺Foxp3⁺调节性T细胞在自身免疫性疾病中的研究进展[J]. 免疫学杂志,2016,32(12):1092-1095.
[22]	周畅,青玉凤,周京国. 调节性T细胞及其在自身免疫性疾病中的研究进展[J]. 山东医药,2015,55(24):96-98.
[23]	聂树涛,李庆,王海燕. 肾综合征出血热患者CD4⁺CD25⁺Foxp3⁺调节性T细胞检测及其意义[J]. 中华医学杂志,2009,89(12):817-819.
[24]	赵淑云. 输卵管癌患者治疗前后及健康女性CD4⁺CD25⁺调节性T细胞数量与功能和免疫抑制因子表达水平比较[J]. 中国妇幼保健,2017,32(10):2099-2101.
[25]	姚晓翠,王静. 炎症性肠病患者体内Treg细胞及TGF-β, IL-10的检测及临床意义[J]. 山东医学高等专科学校学报,2017,39(1):107-110.
[26]	王锁荣,孙志坚,卢建平, 等. 肾综合征出血热患者血清MCP-1, IFN-γ, IL-10, E-选择素和ICAM-1的变化[J]. 江苏医药,2007,33(12):1192-1195.
[27]	孙水林,车达平,郑晓君, 等. 肾综合征出血热10种细胞因子的动态变化及作用机制[J]. 中国人兽共患病学报,2008,24(12):1129-1132.
[28]	高海峰,乔芬,王静. 血清视黄醇结合蛋白,胱抑素C和高半胱氨酸联合检测在早期糖尿病肾病中的诊断价值[J]. 国际检验医学杂志,2013,34(16):2089-2090.
[29]	Hojs R,Bevc S,Ekart R, et al. Serum cystatin C as an endogenous marker of renal function in patients with chronic kidney disease[J]. Renal failure,2008,30(2):181-186.
[30]	宗萍. 肾病综合征出血热早期血清酶变化的临床意义[J]. 中国医药指南,2015,13(28):52-53.
[31]	曾祥文. 肾综合征出血热早期的凝血功能检测及其临床意义[J]. 中国实用医药,2011,6(11):26-27.
[32]	俞建家,张东军,赵宏, 等. 肾综合征出血热血浆P-选择素和组织因子的变化及其与凝血功能紊乱的关系[J]. 河北医药,2014,36(4):488-491.

细胞因子	急性期HFRS患者	恢复期HFRS患者	对照组	χ₁²值	P₁值	χ₂²值	P₂值
IFN-γ	4.182（2.35～11.79）	2.076（1.68～2.92）	1.800（1.57～3.57）	4.273	0.033	3.752	0.053
TNF-α	16.607（14.29～19.21）	14.581（11.98～15.45）	8.500（8.21～11.4）	16.356	< 0.001	13.814	< 0.001
TGF-β1	1.470（1.23～1.76）	2.430（1.93～2.58）	2.500（2.46～2.53）	7.822	0.006	3.000	0.083
IL-6	5.373（2.39～20.42）	2.196（1.181～5.91）	0.990（0.84～1.05）	9.752	0.002	7.9823	0.005
IL-10	13.783（11.00～43.87）	8.961（6.24～15.9）	8.080（6.38～11.1）	6.335	0.012	0.286	0.593

细胞因子	急性期HFRS患者	恢复期HFRS患者	对照组	χ₁²值	P₁值	χ₂²值	P₂值
IFN-γ	4.182（2.35～11.79）	2.076（1.68～2.92）	1.800（1.57～3.57）	4.273	0.033	3.752	0.053
TNF-α	16.607（14.29～19.21）	14.581（11.98～15.45）	8.500（8.21～11.4）	16.356	< 0.001	13.814	< 0.001
TGF-β1	1.470（1.23～1.76）	2.430（1.93～2.58）	2.500（2.46～2.53）	7.822	0.006	3.000	0.083
IL-6	5.373（2.39～20.42）	2.196（1.181～5.91）	0.990（0.84～1.05）	9.752	0.002	7.9823	0.005
IL-10	13.783（11.00～43.87）	8.961（6.24～15.9）	8.080（6.38～11.1）	6.335	0.012	0.286	0.593

检测指标	HFRS急性期[M（Q₁～Q₃）]	HFRS恢复期[M（Q₁～Q₃）]	对照组[M（Q₁～Q₃）]	参考值	χ²值	P值
LDH（U/L）	464.5（353～615）	200.1（182～221）	199.5（161～233）	140～271	52.5	<0.001
Cr（μmol/L）	213.8（118.3～306.6）	82.2（65～90.9）	81.3（62～91.7）	59～104	162.5	<0.001
Cys-C（mg/L）	1.48（1.28～2.36）	1.02（0.86～1.16）	0.97（0.63～1.01）	0.40～1.03	162.5	<0.001
APTT（S）	45.2（39～48.2）	30.3（26.9～32.1）	29.4（23.2～33.0）	21.1～36.5	60.0	<0.001

检测指标	HFRS急性期[M（Q₁～Q₃）]	HFRS恢复期[M（Q₁～Q₃）]	对照组[M（Q₁～Q₃）]	参考值	χ²值	P值
LDH（U/L）	464.5（353～615）	200.1（182～221）	199.5（161～233）	140～271	52.5	<0.001
Cr（μmol/L）	213.8（118.3～306.6）	82.2（65～90.9）	81.3（62～91.7）	59～104	162.5	<0.001
Cys-C（mg/L）	1.48（1.28～2.36）	1.02（0.86～1.16）	0.97（0.63～1.01）	0.40～1.03	162.5	<0.001
APTT（S）	45.2（39～48.2）	30.3（26.9～32.1）	29.4（23.2～33.0）	21.1～36.5	60.0	<0.001

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