Supplementary Material for: The Specific Organism: Not Bacterial Gram Type: Drives the Inflammatory Response in Septic Shock

<b><i>Background and Hypothesis:</i></b> The inflammatory response was targeted by unsuccessful therapies but ignored pathogen. We hypothesized that the inflammatory response differs according to organism in human septic shock. <b><i>Materials and Methods:</i></b> We measured 39 cytokines at baseline and 24 h in patients (<i>n</i> = 363) in the Vasopressin and Septic Shock Trial (VASST). We compared cytokine profiles (cytokine functional class) at baseline and at 24 h by organism and used hierarchical clustering to classify cytokines according to 28-day outcomes. <b><i>Results:</i></b> In 363 patients, 88 and 176 patients had at least 1 species isolated from blood and other sites, respectively. Cytokine levels differed significantly according to organism: <i>Neisseria meningitidis</i> and <i>Streptococcus pneumoniae</i> had the highest (baseline and at 24 h), while <i>Enterococcus faecalis</i> (blood) had the lowest mean cytokine levels. <i>N. meningitidis</i> and <i>Klebsiella pneumoniae</i> had significantly higher cytokine levels at baseline versus 24 h (<i>p</i> = 0.01 and 0.02, respectively); <i>E. faecalis</i> had significantly higher cytokine levels at 24 h versus baseline. Hierarchical clustering heat maps showed that pathogens elicited similar cytokine responses not related to the functional cytokine class. <b><i>Conclusion:</i></b> The organism type induces different cytokine profiles in septic shock. Specific gram-positive and gram-negative pathogens stimulated similar plasma cytokine-level patterns.

<b><i>背景与假说:</i></b> 既往针对炎症反应的治疗均未获得成功，且此类治疗均忽略了病原体的作用。我们提出假说：在人类脓毒性休克中，炎症反应会因病原体种类不同而存在差异。<b><i>材料与方法:</i></b> 本研究针对血管加压素与脓毒性休克试验（Vasopressin and Septic Shock Trial, VASST）中的363例患者，于基线及第24小时检测了39种细胞因子的水平。本研究按病原体种类对比了基线及第24小时的细胞因子谱（细胞因子功能类别），并采用层级聚类法根据28天预后对细胞因子进行分类。<b><i>结果:</i></b> 在363例患者中，分别有88例和176例患者从血液及其他部位分离到至少1种病原体。细胞因子水平因病原体种类不同存在显著差异：脑膜炎奈瑟菌（Neisseria meningitidis）与肺炎链球菌（Streptococcus pneumoniae）患者的细胞因子水平（基线及24小时）最高，而血液来源的粪肠球菌（Enterococcus faecalis）感染患者的平均细胞因子水平最低。脑膜炎奈瑟菌与肺炎克雷伯菌（Klebsiella pneumoniae）感染患者的基线细胞因子水平显著高于24小时水平（分别p=0.01和0.02）；而粪肠球菌感染患者的24小时细胞因子水平则显著高于基线水平。层级聚类热图显示，不同病原体诱导的细胞因子应答模式相似，且该模式与细胞因子的功能类别无关。<b><i>结论:</i></b> 脓毒性休克患者的炎症细胞因子谱因病原体种类不同而存在差异；特定革兰阳性与革兰阴性病原体可诱导相似的血浆细胞因子水平模式。