肾综合征出血热患者血清Th1／Th2细胞因子的变化及临床意义

Dynamic changes and clinical significance of serum Th1/Th2 cytokines in hemorrhagic fever with renal syndrome

目的探讨肾综合征出血热（HFRS）患者血清Th1／Th2细胞因子白细胞介素-12p70（IL—12）、γ干扰素（IFN-γ）、白细胞介素-4（IL-4）的动态变化及其在发病中的作用。方法25例肾综合抓出血热患者（轻症14例、重症11例），按病期（发热期、低血压少尿期、多尿期、恢复期）采集血液标本，分别用酶联免疫吸附试验（ELISA）检测血清IL—12、IFN-γ水平，用放射免疫法检测血清IL-4水平，用全自动生化分析仪检测血尿素氮（BUN）．用血液分析仪计数血小板。结果血清IL—12水平各病期比较变化明显（F=5．765，P〈0．01），与对照组[（0．56±0．10）μg／L]比较，轻、重症组血清IL—12水平在发热期[（0．87±0．38）、（1．08±0．77）μg／L]、低血压少尿期[（0．77±0．21）、（2．11±2．13）μg／L]、多尿期[（1．42±1．10）、（1．20±0．88）μg／L]均见明显升高（P〈0．01）。IFN-γ水平轻、重症组在发热期、低血压少尿期、多尿期分别为（8．04±13．05）、（5．94±8．24），（15．95±18．05）、（4．41±4．10），（1．09±1．24）、（1．38±1．74）μg／L，与对照组（0．27±0．15）μg/L比较明显增高，差异有统计学意义（P〈0．05或〈0.01）。IL-4在病程中变化不明显（F=0．682，P〉0．05）。轻、重症组的IFN—γ与IL-4比值（IFN-γ／IL-4）在发热期[（2．46±3．52）、（16．92±22．77）μg／L]、低血压少尿期[（2．52±2．72）、（1、77±2．06）μg／L]、多尿期[（1．45±2．28）、（2．32±3．98）μg／L]均高于对照组[（0．36±0．26）μg／L]，差异有统计学意义（P〈0．05或〈0．01）。BUN变化趋势与IL—12各病期变化相一致．而与血小板的变化趋势相反。结论肾综合征出血热病程中血清IL—12、IFN-γ7水平增高，IL-4相对不足，存在明显的Th1／Th2平衡失调，是导致全身炎症反应的重要原因，并参与肾综合征出血热的发病机制。

Objective To investigate the changes and pathogenic significance of serum interleukin-12p70 （IL-12）, interfemn-^（IFN-^） and IL-4 in the course of hemorrhagic fever with renal syndrome（HFRS）. Methods Twenty five cases were divided into mild group （14 cases） and severe group （11 cases） according to the severity of illness. Blood samples were collected in various stages （fever, hypotension and oliguria, diuresis stage ）. Serum IL-12 and IFN-γ levels were determined by enzyme-linked immunosorbent assay（ELISA）, IL-4 by radioimmunoassay （RIA）, blood urea nitrogen （BUN） and platelet by automatic biochemical analyzer and blood analyzer. Results Serum IL-12 levels in mild and severe groups were significantly different during various stages of HFRS （F = 5.765, P 〈 0.01 ）. The IL-12 level of both patient groups significantly increased（P 〈 0.01 ） in fever[ （0.87 ± 0.38）, （1.08 ± 0.77）μg/L], hypotension and oliguria [（0.77 ± 0.21 ）, （2.11 ± 2.13）μg/L],and diuresis stage [（1.42 ± 1.10）, （1.20 ± 0.88）μg/L], compared with control group [（0.56 ± 0.10） μg/L]. In various stages, IFN-γ levels of both case groups were respectively （8.04 ± 13.05）, （5.94 ± 8.24）, （15.95 ± 18.05）, （4.41 ± 4.10）, （1.09 ± 1.24）, （1.38 ± 1.74）, （1.12 ± 1.26）, （0.19 ± 1.29）μg/L, and the difference was statistically significant compared with control[ （0.27 ± 0.15 ）μg/L]. IL-4 levels did not change significantly in the stages （F = 0.682,P 〉 0.05）, while the ratios of IFN-γ and IL-4 contents in mild and severe cases were significantly higher than control [ （0.36 ± 0.26） μg/L] in fever[ （2.46 ± 3.52 ）, （16.92 ± 22.77 ）μg/L], hypotension and oliguria [ （2.52 ± 2.72 ）, （1.77 ± 2.06） p.g/L] ,diuresis stage [ （1.45 ± 2.28）, （2.32 ± 3.98）lxg/L], the difference had statically significant （P 〈 0.05 or 0.01）.The curve of IL-12 was similar to that of BUN, but was contrary to blood platelet count. Conclusions The elevated levels of IL-12 and IFN-γ with the imbalance of Th1/Th2 might be the main cause of systemic inflammatory response and involved in the pathogenesis of HFRS.