Mølgaard Asger K, Gasbjerg Kasper S, Mathiesen Ole, Hägi-Pedersen Daniel, Gögenur Ismail
Department of Anaesthesiology, Næstved, Slagelse and Ringsted Hospitals, Research Centre of Anaesthesiology and Intensive Care Medicine, Slagelse, Denmark.
Department of Anaesthesiology, Centre of Anaesthesiological Research, Zealand University, Køge, Denmark.
BMC Anesthesiol. 2025 Mar 21;25(1):136. doi: 10.1186/s12871-025-03003-3.
Pre- and post-operative immune status has gained interest in recent years, as it has been shown to be related to postoperative complications and recovery. The change in immune status has also been known to constitute a large part of the surgical stress response, and it has been speculated that immunomodulatory treatment by glucocorticoids may impact it. Profiling of the impact of specific surgeries and medications on immune status are therefore needed.
We characterized the postoperative blood immune proteome in 83 patients receiving either placebo (n = 20) or IV 24 mg dexamethasone (n = 60) preoperative before total knee arthroplasty (TKA). The primary outcome was the effect of dexamethasone on total knee arthroplasty surgical stress by comparing postoperative immune proteome in the dexamethasone group and the placebo group. Secondary outcomes were the surgical stress by total knee arthroplasty by comparing pre- to postoperative immune proteome in the placebo group, and the combined effect of surgical stress and dexamethasone by comparing pre- to postoperative immune proteome in the dexamethasone group. Characterization was performed with the Olink Explorer Inflammation panel on blood samples from the biobank for future research collected during the randomized, clinical DEX-2-TKA Trial. Protein change was reported as log2-fold-change and p-values were corrected a.m. Benjamini-Hochberg.
The surgical stress (placebo) was characterized by a 4.7 log2-fold-change of IL6 (adjusted p-value < 0.01) and up-regulation of central immune signaling pathways and bone marrow mobilization. The combined effect of surgery and dexamethasone showed a less pro-inflammatory profile: IL6 2.5 log2-fold-change (adjusted p-value < 0.01), with decreased signaling for osteoclast activity and innate, immune cell reaction. The effect of dexamethasone showed upregulation of CSF3 (1.55 log2-fold-change, adjusted p-value < 0.01) and an inhibitory effect on both innate and adaptive immune response, immune cell reactivity and formation of extracellular matrix.
Preoperative dexamethasone indicated anti-inflammatory properties on both innate and adaptive immune response, while surgery was pro-inflammatory. the combination of total knee arthroplasty and dexamethasone inhibited pathways for osteoclast-activity, indicating possible implications on aseptic prosthesis loosening. Dexamethasone showed strong modulation of the surgical stress response following total knee arthroplasty and future studies must explore the clinical associations of these findings.
NCT03506789.
近年来，术前和术后的免疫状态受到了关注，因为已证明其与术后并发症和恢复有关。免疫状态的变化也被认为是手术应激反应的重要组成部分，并且有人推测糖皮质激素的免疫调节治疗可能会对其产生影响。因此，需要分析特定手术和药物对免疫状态的影响。
我们对83例接受全膝关节置换术（TKA）术前接受安慰剂（n = 20）或静脉注射24 mg地塞米松（n = 60）的患者的术后血液免疫蛋白质组进行了表征。主要结果是通过比较地塞米松组和安慰剂组的术后免疫蛋白质组，分析地塞米松对全膝关节置换术手术应激的影响。次要结果是通过比较安慰剂组术前和术后的免疫蛋白质组，分析全膝关节置换术的手术应激，以及通过比较地塞米松组术前和术后的免疫蛋白质组，分析手术应激和地塞米松的联合作用。使用Olink Explorer炎症检测板对生物样本库中在随机临床DEX-2-TKA试验期间收集的血液样本进行表征，以用于未来研究。蛋白质变化以log2倍变化报告，p值采用Benjamini-Hochberg方法进行校正。
手术应激（安慰剂组）的特征是IL6的log2倍变化为4.7（校正p值<0.01），以及中央免疫信号通路和骨髓动员的上调。手术和地塞米松的联合作用显示出炎症反应较轻的特征：IL6的log2倍变化为2.5（校正p值<0.01），破骨细胞活性和先天性免疫细胞反应的信号减少。地塞米松的作用表现为CSF3上调（log2倍变化为1.55，校正p值<0.01），对先天性和适应性免疫反应、免疫细胞反应性以及细胞外基质形成均有抑制作用。
术前地塞米松对先天性和适应性免疫反应均具有抗炎特性，而手术具有促炎作用。全膝关节置换术和地塞米松的联合作用抑制了破骨细胞活性途径，提示可能对无菌性假体松动有影响。地塞米松对全膝关节置换术后的手术应激反应有强烈的调节作用，未来的研究必须探索这些发现的临床关联。
NCT03506789。
