肾综合征出血热10种细胞因子的动态变化及作用机制

Dynamic changes of 10 cytokines in serum of patients with hemorrhagic fever with renal syndrome and its mechanism of action

目的了解10种细胞因子在肾综合征出血热中的动态变化及作用机制。方法前瞻性选取肾综合征出血热病例53例,轻型9例,中型16例,重型15例,危重型13例。按病期采集血清标本,血透治疗时透析前后采集,20例正常人血清作对照;ELISA法检测上述标本中的细胞因子(IL-1β、IL-2、IL-4、IL-6、IL-8、IL-10、IL-12、IL-15、IFN-α和TNF-α);按病期、病型和血透干预3个层次进行分析。结果TNF-α、IL-1β、IL-2、IL-4、IL-6、IL-8、IL-10、IL-12、IL-15在发热期即明显高于对照组,在低血压少尿期达高峰(P<0.01),IFN-α水平在各期均低于对照组(P<0.01);多数细胞因子在重症组高于轻症组(P<0.01);血透后大部分细胞因子有明显下降(P<0.01)。结论10种细胞因子均参与肾综合征出血热发病的炎症过程;促炎与抗炎介质分泌失衡,TNF-α、IL-1β、IL-2、IL-4、IL-6、IL-8、IL-10、IL-12和IL-15分泌过量、导致明显的全身炎症反应,分泌量与炎症损害呈正相关;IFN-α分泌不足,可能导致细胞免疫功能受限,不利于炎症的控制;血透能显著减少患者血清中的细胞因子、减轻炎症损害。

To observe the changes of 10 cytokines in serum of patients with hemorrhagic fever with renal syndrome （HFRS） and to evaluate its mechanism of action, 53 cases of patients with HFRS were prospectively selected for study, including 9 mild cases, 16 moderate eases, 15 severe eases and 13 dangerous cases. Serum samples of patients were collected at different stages of disease, both before and after treatment with hematodialysis. Meanwhile. 20 healthy adults were selected as normal controls. The serum levels of cytokines （IL-1β, IL-2, IL-4, IL-6. IL-8. IL-10, IL-12, IL-15, IFN-α and TNF-α were detected by ELISA assay and the results were analyzed according to 3 items; stage and pattern of disease as well as the effect of intervention with hematodialysis. Compared with the normal controls, the serum levels of these cytokines tested were significantly elevated in HFRS patients during febrile stage with peak values in the hypotensive-oligourie stage （P〈0. 01）. It is evident that these 10 kinds of cytokines may be associated with the development of inflammation in HFRS during febrile stage, in which the pro-inflammatory and anti-inflammatory eytokines may be under an unbalanced status. The over secretion of cytokines TNF-α, IL-1β, IL-2. IL-4, IL-6, 1L-8,IL-10, IL-12 and IL-15 may lead to the development of systemic inflammatory reactions, whereas the insufficient secretion of IFN-α may limit the function of cell-mediated immunity which is unsuitable for the control of inflammation. As to the effect of hematodialysis, it seems to decrease the amounts of cytokines secreted ,thus lessening the damages induced by inflammation.