重度烧伤患者血清白细胞介素6、10含量变化与脓毒症发生及预后的相关性研究

Changes in serum contents of interleukin-6 and interleukin-10 and their relation with occurrence ofsepsis and prognosis of severely burned patients

目的 观察重度烧伤患者血清IL-6、IL-10含量的变化，探讨其与脓毒症发生及预后的关系。 方法选择2007年3月-2011年3月笔者单位收治的160例大面积严重烧伤成年患者，伤后（1.0±6．O）h入院。根据患者脓毒症发生及死亡情况，将其分为非脓毒症组112例、脓毒症存活组36例、脓毒症死亡组12例，后2组患者脓毒症发生时间为伤后（9±5）d，脓毒症死亡组于伤后（18±4）d死亡。另选择20例成年健康志愿者作为健康对照组。分别统计比较4组受试人员的年龄、3组患者烧伤总面积和Ⅲ度烧伤面积。于各例患者入院后（伤后1 d）至伤后20 d每日采血分离血清，用ELISA法测定IL-6、IL-10含量；同法采集健康对照组人员血液检测此2项指标。受试者一般资料数 据采用单凶素方差分析，IL-6、IL-10含量数据采用重复测量资料的方差分析及SNK法（q检验）。结果 （1）3组烧伤患者与健康对照组人员年龄接近（F=2.090，P〉0.05），2个脓毒症组患者烧伤总面积明显大于非脓毒症组（g检验P值均小于0. 05），脓毒症死亡组烧伤总面积明显大于脓毒症存活组（q检验P〈 0.05）。2个脓毒症组Ⅲ度面积明昱大于非脓毒症组（q检验P值均小于0.05）。（2）3组患者伤后1—20 d血清IL-6含量均明显高于健康对照组。伤后1～7 d3组患者IL-6含量接近（F值为0. 188~2.897，P值均大于0.05）。伤后第4天起非脓毒症组IL-6含量开始下降；13 d起脓毒症存活组IL-6含量逐渐下降，而同期脓毒症死亡组IL-6含量继续升高。伤后8d起，非脓毒症组 IL-6含量[第8天为（262±25） pg/mL]明显低于脓毒症存活组[第8天为（287 ±38） pg/mL，q检验P〈0. 05]和脓毒症死亡组[第8天为（299±22） pg/mL，q检验P〈0.05]。伤后13 d起，脓毒症存活组IL-6含量[第13天为（300 ±33） pg/mL]明显低于脓毒症死亡组[第13天为（338±22） pg/mL，q检验P〈 0.05]。（3）3组烧伤患者各时相点IL-10含量均高于健康对照组。伤后1—5 d，3组烧伤患者该指标水平接近（F值为1. 802~2.538，P值均大于0.05）；第6天起，非脓毒症组IL-10含量明显低于脓毒症死亡组（q检验P值均小于0. 05）。伤后第8天，脓毒症存活组IL-10含量为（54±19） pg/mL．显著低于脓毒症死亡组[（ 91 ±23） pg/mL，q检验P〈0.05]，根据此结果计算出IL-10含量临界值设 为77 pg/mL时，灵敏度（83. 33%，10/12）与特异度（91. 67%，33/36）之和减1值最大，可用于判断脓毒症结局。 结论在烧伤患者年龄相近的情况下，脓毒症的发生和结局与烧伤面积、深度有关。血 清IL-6、IL-10含量在烧伤脓毒症发病机制中均起重要作用。早期IL-6含量不宜用于判断脓毒症患者预后；早期IL-10含量持续高于77 pg/mL提示患者预后不良。

Objective To ohserve山e changes in serum contents of interleukin-6 （IL-6） and inter-leukin-10 （11-10） in patients with severe burn injury, and to investigate their relaLion with occurrence of sepsis and prognosis of patients. Methods One-hundred and sixty adult patients admitted into our hospi-tal （1.0 ＋6.0） h after injury during March 2007 to March 2011 with massive and severe burns were enrolled in the investigation. Patients were divided into non-sepsis group （ NS, n, = 112） , sepsis-survival group（ SS, n = 36） , and sepsis-deceased group （ SD, n, = 12） based on the occurrence of sepsis and death. Sepsis occurred on post burn day （ PBD） 9 ＋5 in patients in the latter Lwo groups. Patients died on PBD 18 ＋4 in SD group. Twenty healthy adult volunteers were chosen as healthy control group （ HC）. The age of sub-jects for observation among four groups, and total burn area and full-thickness burn area of patients among NS, SS, and SD groups were compared. Serum was isolated from hlood samples collected from each patient every day from day of admission till PBD 20 to determine the contents of IL-6 and IL-10 by ELISA, and the same determinations were done in HC group. Data of trial subjec：ts were processed with one-way analysis of variance. Data of IL-6 and IL-10 contents were processed with analysis of variance of repeated measure data and SNK method （ q test）. Results （1） There was no signific,ant statistic,al difference among four groups in age （ F = 2. 090, P 〉 0. 05）. Total burn areas of patients in SS and SD groups were significantly larger than that in NS group （ q test, with P values hoth below 0. 05） , and total burn area of patients in SD group was ohviously larger than that in SS group （ q test, P 〈 0. 05 ） . Full-thic,kness hurn areas of patients in SS and SD groups were signific：antly larger than that in NS group （ q test, with P values both below 0. 05 ） . （2） Serum c：ontents of＇ IL-6 0f patients in NS, SS, and SD groups from PBD l t0 20 were obviously higher than that of volunteers in HC group. There was no signific,ant statistic,al difference among NS, SS, anci SD groups in serum contents of＇ IL-6 from PBD l t0 7 （ with F value f＇rom 0. 188 t0 2. 897, P values all ahove 0. 05 ）. Serum c：ontent of IL-6 0f patients in NS group dec：reased from PBD 4. Serum content of IL-6 0f patients in SS group decreased gradually from PBD 13, but that in SD group increased continuously at Lhe same time points. Serum c,ontents of IL-6 0f paLients in NS group [ （262 ＋ 25） pg/mL on PBD 8] were lower than those in SS group [ （287 ＋38） pg/ruL on PBD 8, q test, P 〈0. 05 ] and SD group [ （299 ＋22） pg/mL on PBD 8, q test, P 〈 0. 05 ] from PBD 8. Serum contents of IL-6 0f patients in SS group [ （300 ＋33） pg/mL on PBD 13] were obviously lower than those in SD group [（338 ＋22） pg/mL on PBD 13, q test, P 〈 0. 05] from PBD 13. （3） Serum contents of IL-10 0f patients in NS, SS, and SD groups were higher than that in HC group at each time point. There was no significanc statistic,al differenc,e among NS, SS, and SD groups in serum contents of IL-6 from PBD l t0 5 （ with F values from l. 802 t0 2. 538, P values all above 0. 05） . Serum content of IL-10 0f patients in NS group was ohviously lower than that of patients in SD group from PBD 6 （ q test, P values all below 0. 05）. On PBD 8, serum c：ontent of IL-10 0f patients in SS group [ （ 54 ＋ 19） pg/mL] was ohviously lower chan that in SD group [ （ 91 ＋ 23 ） pg/mL, q test, P 〈 0. 05 ] . The sum of sensitivity （83. 33% , 10/12） and specific,ity （91. 67% , 33/36） minus l was maximum when the critical value of IL-10 content was set at 77 pg/mL based on the comparison between SS group and SD group in serum c,ontent of IL-10 0n PBD 8. Conclusions The oc：c：urrenc,e and outcome of sepsis is related to burn area and depth when the patients are in similar age. Serum contents of IL-6 and IL-10 play important roles in the pathogenesis of sepsis after hurn. IL-6 content in early stage shall not he used in predicting che prognosis of patients with sepsis. IL-10 continuously higher than 77 pg/mL in early stage forecasts unfavorable prognosis of patient.