促炎与抗炎细胞因子在肾综合征出血热发病中的作用

Changes of pro-and anti-inflammatory cytokines and their pathogenic significance in hemorrhagic fever with renal syndrome

目的了解肾综合征出血热患者促炎与抗炎细胞因子的变化在其发病中的作用。方法将35例患者分为轻症组19例，重症组16例，按病期采血，分别用ELISA和放射免疫法检测细胞内黏附分子（ICAM）-1、E-选择素、L-选择素、转化生长因子（TGF）β-1、IFN-γ、TNF-α、IL-18、IL-2、IL-4、IL-10等细胞因子，并同期检测PLT和肾功能。结果从发热期至多尿期，血清TNF-α、IL-1β、IFN-γ、IL-2、E-选择素、L-选择素和ICAM-1水平均高于对照组（P〈0．05或P〈0．01），而IL-4、TGF-β1则显著降低，血清IL-10增幅比IFN-γ低，以致IFN-γ／IL-10比值显著增高；TNF-α、IFN-γ与BUN呈一致性变化趋势，而与PLT变化趋势相反。结论肾综合征出血热发病过程中存在促炎与抗炎细胞因子的失衡，这种失控性炎症反应是引起毛细血管渗漏和多器官功能障碍综合征的主要机制。合理补液、适量使用免疫调节剂，尽快恢复促炎与抗炎的平衡，可望改善本病的预后。

Objective To investigate the changes of serum pro-and anti-inflammatory cytokines and their pathogenic significance in hemorrhagic fever with renal syndrome （HFRS）. Methods Serum levels of E-selectin, L-selectin, intercellular adhesion molecule （ICAM） 1, transfoming growth factor（TGF）β-1, IFN-γ, TNF-α, IL-1β, IL-2, IL-4 and IL 10 were detected by ELISA and radioim munoassay respectively in 35 HFRS patients（19 mild cases and 16 severe cases）at different disease stages. Blood urea nitrogen（BUN）and platelet count were examined simultaneously. Results Serum levels of TNF-α, IL-1β, IFN-γ, IL-2, E-selectin, L-selectin and ICAM 1 in HFRS cases were significantly increased during febrile stage to polyuric stage, compared with control group（ P 〈 0. 05 or 0. 01, respectively）. On the contrary, serum IL 4 and TGFβ- 1 levels were significantly decreased. As the increase of serum IFN-γ level was much higher than the increase of IL-10 level, the ratio between IFN-γ and IL 10 was remarkably elevated. The tendency of TNF-α and IFN-γ levels were positively correlated with the change of BUN, but inversely correlated with the change of blood platelet count. Conclusions During the course of HFRS, the up-regulation of pro-inflammatory cytokines significantly exceeds over that of anti-inflammatory cytokines, which can contribute to the pathogenesis of capillary leakage and multiple organ dysfunction syndrome（MODS）. Thus, prompt and appropriate treatment with fluid replacement and immunoregulators that can restore the balance between pro-and anti-inflammatory cytokines may improve the prognosis of this disease.