Hildebrand Frank, Stuhrmann Manfred, van Griensven Martijn, Meier Sven, Hasenkamp Sandra, Krettek Christian, Pape Hans-Christoph
Trauma Department, Medical School Hannover, Carl-Neuberg Strasse 1, 30625 Hannover, Germany.
Cytokine. 2007 Mar;37(3):192-9. doi: 10.1016/j.cyto.2007.03.008. Epub 2007 May 10.
Interleukin-8 (IL-8) is regarded as one of the most important mediators in the pathogenesis of Adult Respiratory Distress Syndrome (ARDS). However, knowledge regarding the influence of genetic variations within the IL-8 gene either on the development of ARDS or on IL-8 production in the traumatic setting is sparse.
In this prospective cohort study, patients were included if the following criteria were fulfilled: Injury Severity Score (ISS) >16, age 18-60 years and a survival >48 h after injury. Systemic IL-8 concentrations and the polymorphisms (IL-8-251A/T) were determined. Patients were separated according to the development of ARDS (group +ARDS vs. group -ARDS) and the genotypes of the IL-8-251A/T polymorphism (genotypes A/A, A/T and T/T).
Group +ARDS demonstrated significantly higher IL-8 plasma concentrations from day 3 until the end of the observation period compared to group -ARDS. In addition, duration of mechanical ventilation and length of stay in the ICU were significantly longer in this group. Furthermore, a significant association between the IL-8-251A allele and IL-8 production (day 4-8) was observed. Genotype A/A showed a significantly longer duration of mechanical ventilation compared to genotype T/T. A trend towards an association between the IL-8-251A allele and an increased incidence of posttraumatic ARDS was observed (p=0.08).
This data reaffirms a central role of IL-8 in the pathogenesis of ARDS. Furthermore, it points towards a genetic predisposition for posttraumatic IL-8 synthesis which might also be associated with the development of posttraumatic ARDS.
白细胞介素-8(IL-8)被认为是成人呼吸窘迫综合征(ARDS)发病机制中最重要的介质之一。然而,关于IL-8基因内的遗传变异对ARDS发生发展或创伤情况下IL-8产生的影响的了解却很少。
在这项前瞻性队列研究中,符合以下标准的患者被纳入研究:损伤严重程度评分(ISS)>16,年龄18 - 60岁,伤后存活>48小时。测定全身IL-8浓度和多态性(IL-8 - 251A/T)。根据ARDS的发生情况(+ARDS组与-ARDS组)和IL-8 - 251A/T多态性的基因型(A/A、A/T和T/T基因型)对患者进行分组。
与-ARDS组相比,+ARDS组从第3天到观察期结束时IL-8血浆浓度显著更高。此外,该组机械通气时间和在重症监护病房的住院时间显著更长。此外,观察到IL-8 - 251A等位基因与IL-8产生(第4 - 8天)之间存在显著关联。与T/T基因型相比,A/A基因型的机械通气时间显著更长。观察到IL-8 - 251A等位基因与创伤后ARDS发病率增加之间存在关联趋势(p = 0.08)。
这些数据再次证实了IL-8在ARDS发病机制中的核心作用。此外,它表明创伤后IL-8合成存在遗传易感性,这也可能与创伤后ARDS的发生有关。