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Dynamic changes in blood cytokine levels as clinical indicators in severe acute respiratory syndrome
作者姓名:Beijing  Group  of  National  Research  Project  for  SARS
作者单位:Beijing Group of National Research Project for SARS: Beijing Institute of Respiratory Medicine, Beijing Chaoyang Hospital,Capital University of Medical Sciences (Pang BS, Wang Z, Zhang LM, Tong ZH, Xu LL, Huang XX, Guo WJ, Zhu M, Wang C); Beijing Ditan Hospital (Li XW, He ZP, Li HX, Zhao FJ)
基金项目:The study was sponsored by the National Research Project for SARS (No. 2003AA208102).
摘    要:Objective To investigate the dynamic changes observed in serum levels of interleukins (ILs), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in severe acute respiratory syndrome (SARS) patients.Methods Sixty-one cases of SARS with positive antibodies to SARS coronavirus (SARS-CoV) were classified into the following categories: initial stage (3-7 days), peak stage (8-14 days), and remission and recovery stage (15-27 days). Forty-four healthy individuals were used as controls. Serum levels of ILs, TNF-α and TGF-β1 were measured in all subjects. Serum antibodies to SARS-CoV were detected only in SARS cases. Results The mean concentration of serum IL-6 in SARS patients did not differ from that in the control group in initial and peak stages, but became significantly higher in remission and recovery stage compared with the control group, initial and peak stages (P<0.01). The mean concentration of serum IL-8 in SARS patients did not differ from that of the control group in initial stage, but was significantly higher than control group in peak stage and remission and recovery stage (P<0.05). And it was more significantly higher in remission and recovery stage than in peak stage (P<0.01). The mean concentrations of IL-16 and TNF-α in SARS patients were higher than those of the control group for every length of the clinical courses investigated, and were especially high in remission and recovery stage (P<0.01). SARS patients experienced higher concentration of serum IL-13 compared with the controls in initial stage (P<0.01), but returned to normal levels in peak stage and in remission and recovery stage. The mean concentration of serum IL-18 in SARS patients was significantly lower than that of the control group during all clinical courses (P<0.05). The mean concentration of serum TGF-β1 in SARS patients was higher than that of the control group during all clinical courses. Although TGF-β1 in serum decreased in remission and recovery stage in SARS patients, the average was still higher than that of the control group (P<0.01).Conclusions Most proinflammatory cytokines and TGF-β1 were elevated during the early phase of SARS, which may be associated with lung infiltration and proliferation. Concurrently, the mean concentration of serum IL-13 decreased gradually, and the mean concentration of serum IL-18 level in SARS patients was lower than that of the control group during all the courses of SARS, suggesting that the immune state of the patients with SARS was obviously abnormal. Observing the dynamic changes in blood cytokine levels can provide a scientific basis to assess pathogenesis and efficacy of clinical treatment of SARS.

关 键 词:严重急性呼吸综合征  肿瘤坏死因子-α  白细胞介素  转化生长因子-β1

Dynamic changes in blood cytokine levels as clinical indicators in severe acute respiratory syndrome
Beijing Group of National Research Project for SARS.Dynamic changes in blood cytokine levels as clinical indicators in severe acute respiratory syndrome[J].Chinese Medical Journal,2003,116(9):1283-1287.
Authors:Beijing Group of National Research Project for SARS
Abstract:Objective To investigate the dynamic changes observed in serum levels of interleukins (ILs), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in severe acute respiratory syndrome (SARS) patients.Methods Sixty-one cases of SARS with positive antibodies to SARS coronavirus (SARS-CoV) were classified into the following categories: initial stage (3-7 days), peak stage (8-14 days), and remission and recovery stage (15-27 days). Forty-four healthy individuals were used as controls. Serum levels of ILs, TNF-α and TGF-β1 were measured in all subjects. Serum antibodies to SARS-CoV were detected only in SARS cases. Results The mean concentration of serum IL-6 in SARS patients did not differ from that in the control group in initial and peak stages, but became significantly higher in remission and recovery stage compared with the control group, initial and peak stages (P<0.01). The mean concentration of serum IL-8 in SARS patients did not differ from that of the control group in initial stage, but was significantly higher than control group in peak stage and remission and recovery stage (P<0.05). And it was more significantly higher in remission and recovery stage than in peak stage (P<0.01). The mean concentrations of IL-16 and TNF-α in SARS patients were higher than those of the control group for every length of the clinical courses investigated, and were especially high in remission and recovery stage (P<0.01). SARS patients experienced higher concentration of serum IL-13 compared with the controls in initial stage (P<0.01), but returned to normal levels in peak stage and in remission and recovery stage. The mean concentration of serum IL-18 in SARS patients was significantly lower than that of the control group during all clinical courses (P<0.05). The mean concentration of serum TGF-β1 in SARS patients was higher than that of the control group during all clinical courses. Although TGF-β1 in serum decreased in remission and recovery stage in SARS patients, the average was still higher than that of the control group (P<0.01).Conclusions Most proinflammatory cytokines and TGF-β1 were elevated during the early phase of SARS, which may be associated with lung infiltration and proliferation. Concurrently, the mean concentration of serum IL-13 decreased gradually, and the mean concentration of serum IL-18 level in SARS patients was lower than that of the control group during all the courses of SARS, suggesting that the immune state of the patients with SARS was obviously abnormal. Observing the dynamic changes in blood cytokine levels can provide a scientific basis to assess pathogenesis and efficacy of clinical treatment of SARS.
Keywords:severe acute respiratory syndrome  pneumonia  interleukins  tumor necrosis factors  transforming growth factors
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