Saha Priyanka, Das Deepanwita, Behera Santosh Kumar, Bhatia Deepak, Kumar Sunil, Hajra Srabanti, Das Dipkana, Chakrabarti Deepa, Sinha Dona
Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, Kolkata, India.
Department of Anesthesiology, Chittaranjan National Cancer Institute, Kolkata, India.
Indian J Med Res. 2024 Nov;160(5):489-500. doi: 10.25259/jmr_2382_23.
Background & objectives The choice of anesthetic for better perioperative conservation of immune responses has always been contentious. This study investigated the differential impact of the intravenous anesthetic, propofol, and the volatile anesthetic, isoflurane on the T cell immune responses, if any, among individuals going through perioperative breast cancer. Methods Perioperative blood samples (preoperative, intraoperative and postoperative) collected from participants with breast cancer in two arms namely isoflurane arm (n=50) and the propofol arm (n=50) were analyzed for T cell immune response using flow cytometry and ELISA. The interactions of anesthetics with CD4/CD8 were probed with molecular docking and molecular dynamic (MD) simulations. Results Linear mixed model analysis showed that isoflurane in comparison to propofol inhibited CD4+ helper (Th) [β-coefficient: -8.75; 95% CI: -13.00 to -4.51] and CD19+ B cell (β: -7.51; 95% CI: -15.46 to 0.44) frequencies during the intraoperative period in perioperative breast cancer patients. Further, interleukin (IL)-10 and IL-12 were significantly increased during the intra- and postoperative periods in the isoflurane group as compared to the propofol group. Molecular docking (MD) validated propofol's better binding energy with CD4/CD8 than isoflurane. MD simulations propagated that in contrast to isoflurane, propofol formed a more compact and stabilized structure with CD4/CD8, making the amino acid residues on the surface of CD4/CD8 inaccessible for any interaction. Interpretation & conclusions The clinical observations and the in silico findings exhibited that propofol in comparison to isoflurane better regulated T cell immuno-inflammatory response in perioperative breast cancer patients.
背景与目的 选择能在围手术期更好地保护免疫反应的麻醉剂一直存在争议。本研究调查了静脉麻醉剂丙泊酚和挥发性麻醉剂异氟烷对接受围手术期乳腺癌治疗的个体的T细胞免疫反应的差异影响（若有）。方法 从乳腺癌患者的两个组（异氟烷组，n = 50；丙泊酚组，n = 50）收集围手术期血样（术前、术中和术后），使用流式细胞术和酶联免疫吸附测定法分析T细胞免疫反应。通过分子对接和分子动力学（MD）模拟探究麻醉剂与CD4/CD8的相互作用。结果 线性混合模型分析表明，与丙泊酚相比，异氟烷在围手术期乳腺癌患者的术中抑制了CD4 + 辅助性（Th）细胞[β系数：-8.75；95%置信区间：-13.00至-4.51]和CD19 + B细胞（β：-7.51；95%置信区间：-15.46至0.44）的频率。此外，与丙泊酚组相比，异氟烷组在术中和术后白细胞介素（IL）-10和IL-12显著增加。分子对接（MD）验证了丙泊酚与CD4/CD8的结合能比异氟烷更好。MD模拟表明，与异氟烷相比，丙泊酚与CD4/CD8形成了更紧密和稳定的结构，使CD4/CD8表面的氨基酸残基无法进行任何相互作用。解读与结论 临床观察和计算机模拟结果表明，与异氟烷相比，丙泊酚能更好地调节围手术期乳腺癌患者的T细胞免疫炎症反应。
