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

Change of tumor necrosis factor α,interferon γ,interleukin-10 and transforming growth factor-β1 in hemorrhagic fever with renal syndrome

目的研究肾综合征出血热患者血清肿瘤坏死因子α(TNFα)、干扰素γ(IFNγ)、白细胞介素-10(IL-10)、转化生长因子-β1(TGF-β1)的变化及其在发病中的作用。方法按病期采集血标本,用放射免疫法检测TNFα和IL-10,用酶联免疫吸附试验(ELISA)检测IFNγ和TGF-β1,并同步作血小板计数和肾功能检测。结果从发热期至恢复初期血清TNFα与IFNγ均高于正常水平,以低血压少尿期为最著;轻症组IFNγ水平略高于重症组;与此相反,血清TGF-β1水平于病程前4期均见下降,直至恢复期才见回升;血清IL-10水平在病程中也见增高,但升高幅度不及IFNγ;在发热期和低血压少尿期血清IFNγ/IL-10比值分别为0.26±0.35与0.72±0.93,均显著高于对照组(0.10±0.16)水平,其变化曲线与BUN相一致,而与血小板呈负相关。结论TNFα、INFγ等细胞因子的过多释放以及辅助性T细胞(Th1/Th2)失平衡参与了HFRS的发病机制,采取合理的对症治疗、维持促炎与抗炎系统的平衡可能有利于病情的恢复。

Objective To investigate the change of serum tumor necrosis factor α（TNFα） ,interferon γ（IFNγ）, interleukin-10（IL-10） and transforming growth factor-β1 （TGF-β1） in the patients of hemorrhagic fever with renal syndrome（HFRS） and to evaluate their significance in the pathogenesis of HFRS. Methods Blood samples were eollected at different stages of the disease, TNFα and IL-10 were detected by radioimmunoassay（RIA）, IFNγ and TGF- β1 by enzyme-linked immunosorbent assay （ELISA）, platelet was counted and renal function tested by automatic biochemical analyzer. Results The concentrations of TNFα and IFNγ were significantly increased in all the phases of the disease with the peak values in hypotensive-oliguric stages,and the levels of IFNγ in moderate group were slightly higher than those in severe group. On the contrary, the levels of serum TGF-β1 were reduced significantly during the first four phases. As a whole, IL-10 levels were also elevated in the course of HFRS, but the excessive grade was much lower in IL-10 than in IFNγ, and the ratios of IFNγ/IL-10 in febrile stage （0.26 ± 0.35） and in hypotensive-oliguric stage （0.72±0.93） were significantly higher than that （0.10±0.16） in control group. The curve of IFNT/IL-10 ratios was consistent with the change of BUN,but was contrary to that of platelet count. Conclusions The excessive release of TNFα and IFNγ and the imbalance of Th1 / Th2 might contribute to the pathogenesis of HFRS, hence the reasonable symptomatic therapy to maintain the balance between pro- and anti-inflammatory responses might be beneficial to the patients with HFRS.