BACKGROUND Coagulase-negative staphylococci (CoNS) such as Staphylococcus epidermidis are highly prevalent pathogens for sepsis in neonates. The interaction between host, environment and pathogenic factors of S. epidermidis are still poorly understood. Our objective was to address the role of several pathogenic factors of S. epidermidis on neonatal cytokine responses and to characterize the influence of three immunomodulatory drugs. METHODS We performed an ex-vivo model of S. epidermidis sepsis by assessment of blood cytokine production in neonatal whole blood stimulation assays (ELISA). S. epidermidis strains with different characteristics were added as full pathogen to umbilical cord blood cultures and the influence of indomethacin, ibuprofen and furosemide on neonatal immune response to S. epidermidis was evaluated (Flow cytometry). RESULTS Stimulation with S. epidermidis sepsis strains induced higher IL-6 and IL-10 expression than stimulation with colonization strains. Biofilm formation in clinical isolates was associated with increased IL-10 but not IL-6 levels. In contrast, stimulation with mutant strains for biofilm formation and extracellular virulence factors had no major effect on cytokine expression. Notably, addition of ibuprofen or indomethacin to S. epidermidis inoculated whole blood resulted in mildly increased expression of TNF-α but not IL-6, while frusemide decreased the production of pro-inflammatory cytokines, i.e. IL-6 and IL-8. CONCLUSIONS The virulence of sepsis strains is coherent with increased cytokine production in our whole-blood in-vitro sepsis model. Biofilm formation and expression of extracellular virulence factors had no major influence on readouts in our setting. It is important to acknowledge that several drugs used in neonatal care have immunomodulatory potential.

中文翻译：

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新生儿全血中表皮葡萄球菌诱导的先天免疫反应的调节。

背景技术凝固酶阴性葡萄球菌（CoNS）如表皮葡萄球菌是新生儿败血症的高度流行病原体。表皮葡萄球菌的宿主，环境和致病因素之间的相互作用仍然知之甚少。我们的目标是解决表皮葡萄球菌的几种致病因素对新生儿细胞因子反应的作用，并表征三种免疫调节药物的影响。方法我们通过评估新生儿全血刺激试验（ELISA）中血液细胞因子的产生，建立了表皮葡萄球菌败血症的离体模型。将具有不同特征的表皮葡萄球菌菌株作为完整病原体添加到脐带血培养物中，并评价了吲哚美辛，布洛芬和呋塞米对新生儿对表皮葡萄球菌免疫反应的影响（流式细胞术）。结果表皮葡萄球菌败血症菌株刺激比定殖菌株刺激诱导更高的IL-6和IL-10表达。临床分离物中生物膜的形成与IL-10水平升高有关，但与IL-6水平无关。相反，用突变菌株刺激生物膜形成和细胞外毒力因子对细胞因子表达没有重大影响。值得注意的是，向表皮葡萄球菌接种的全血中添加布洛芬或吲哚美辛可导致TNF-α的表达轻度增加，但不会导致IL-6的表达轻度增加，而氟塞米可降低促炎细胞因子（即IL-6和IL-8）的产生。结论在我们的全体外脓毒症模型中，脓毒症菌株的毒力与细胞因子产生的增加相关。在我们的环境中，生物膜的形成和细胞外毒力因子的表达对读数没有重大影响。必须承认，新生儿护理中使用的几种药物具有免疫调节潜力。