Abstract：
Reliable methods to assess immune function after solid organ transplantation (SOT) are needed to guide dosing of immunosuppression. We hypothesized that toll-like receptor ligand-induced cytokine concentrations would decrease post-transplantation due to the use of immunosuppressive medication. Furthermore, we hypothesized that induced cytokine concentrations pre-transplantation would be higher in recipients with episodes of acute rejection post-transplantation due to underlying immunological dispositions. We aimed to investigate toll-like receptor ligand-induced cytokine concentrations by TruCulture©, a standardized immunoassay, in SOT recipients before and 3 months after SOT and explored associations with methylprednisolone-treated acute rejections. We conducted a prospective, observational cohort study including 123 participants (67 liver, 32 kidney and 24 lung transplant recipients). Whole blood was stimulated for 22 h with: (A) Lipopolysaccharide (LPS), (B) Resiquimod, (C) Polyinosinic:polycytidylic acid (Poly I:C) and (D) a blank control. Cytokine concentrations (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, IFN-α and IFN-γ) were measured by Luminex. 30 participants developed methylprednisolone-treated acute rejection at a median of 9 days (IQR 5-17) post-SOT. We found that all induced cytokine concentrations decreased post-SOT except from LPS-induced and Poly I:C-induced IL-10. The induced cytokine concentration pre-transplantation did not differ in recipients with or without acute rejection. In conclusion, the induced cytokine concentrations decreased for all stimuli post-SOT, except the anti-inflammatory cytokine IL-10. Importantly, recipients developing early acute rejection did not differ in induced cytokine concentrations pre-SOT. Thus, the use of a standardized assay in SOT is feasible in a clinical setting and may provide important information on the immune function post-SOT.
摘要：
需要可靠的方法来评估实体器官移植（SOT）后的免疫功能，以指导免疫抑制的给药。我们假设由于使用免疫抑制药物，Toll样受体配体诱导的细胞因子浓度会降低移植后。此外，我们假设,由于潜在的免疫倾向,在移植后发生急性排斥反应的受者中,移植前诱导的细胞因子浓度会更高.我们旨在通过TruCulture©研究Toll样受体配体诱导的细胞因子浓度，标准化的免疫测定，在SOT之前和之后3个月的SOT接受者中，并探讨了与甲基强的松龙治疗的急性排斥反应的关系。我们进行了一个前瞻性的，观察性队列研究，包括123名参与者(67名肝脏，32名肾脏和24名肺移植受者)。用以下方法刺激全血22小时:(A)脂多糖(LPS),(B)雷喹莫特，(C)聚肌苷酸:聚胞苷酸(聚I:C)和(D)空白对照。细胞因子浓度（TNF-α，IL-1β,IL-6、IL-8、IL-10、IL-12p40、IL-17A、通过Luminex测量IFN-α和IFN-γ）。30名参与者在SOT后9天（IQR5-17）出现甲基强的松龙治疗的急性排斥反应。我们发现，所有诱导的细胞因子浓度均在SOT后降低，但LPS诱导的和PolyI：C诱导的IL-10除外。移植前诱导的细胞因子浓度在有或没有急性排斥的接受者中没有差异。总之,SOT后所有刺激的诱导细胞因子浓度降低，除了抗炎细胞因子IL-10。重要的是,发生早期急性排斥反应的受者在SOT前的诱导细胞因子浓度没有差异.因此，在SOT中使用标准化测定在临床环境中是可行的,并且可以提供关于SOT后免疫功能的重要信息.
