Suppressive effect of the anesthetic Propofol on the T cell function and T cell-dependent immune responses
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ABSTRACT:
PROVIDER: PRJNA1117397 | ENA |
REPOSITORIES: ENA
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Project description:General anesthesia is thought to suppress the immune system and negatively affect postoperative infection and the long-term prognosis of cancer. However, the mechanism underlying immunosuppression induced by general anesthetics remains unclear. In this study, we focused on propofol, which is widely used for sedation under general anesthesia and intensive care and examined its effects on the T cell function and T cell-dependent immune responses. We found that propofol suppressed T cell glycolytic metabolism, differentiation into effector T cells, and cytokine production by effector T cells. CD8 + T cells activated and differentiated into effector cells in the presence of propofol in vitro showed reduced antitumor activity. Furthermore, propofol treatment suppressed the increase in the number of antigen-specific CD8 + T cells during Listeria infection. In contrast, the administration of propofol improved inflammatory conditions in mouse models of inflammatory diseases, such as OVA-induced allergic airway inflammation, hapten-induced contact dermatitis, and experimental allergic encephalomyelitis. These results suggest that propofol may reduce tumor and infectious immunity by suppressing the T cell function and T cell-dependent immune responses while improving the pathogenesis and prognosis of chronic inflammatory diseases by suppressing inflammation.
2025-08-25 | GSE268453 | GEO
Project description:Propofol is an intravenous anesthetic that has been widely used in the clinical setting. Besides its anesthetic effects, propofol has been reported to influence the regulation of autonomic system. Controversies exist with regards to whether propofol exposure is safe for pregnant women and young children. The recent emergence of human induced pluripotent stem cells (hiPSCs) has provided a promising and theoretically inexhaustible source of neural progenitor cells (NPCs) for drug testing, which could be extended to in vitro experiments for anesthetics such as propofol. NPCs derived from three hiPSC lines, NES-GFP (a NESTIN-GFP reporter), USCK7 (iPSCs derived from urine derived cells), and ND2-0 (NIH), were treated with propofol at different concentrations (20, 50, 100 and 300 µM) for 6 h or 24 h. Early and late cell injury, cell proliferation and apoptosis were evaluated. Comparison of genome-wide gene expression profiles was performed for propofol-treated and untreated control iPSC-NPCs. Propofol treatment of NPCs for 6 h at the clinically relevant concentration (20 or 50 µM) did not affect cell viability, apoptosis, or proliferation, while propofol at higher concentration (100 or 300 µM) decreased NPC viability and induced apoptosis. Prolonged treatment of propofol for 24 h significantly decreased cell viability. In addition, 20 µM propofol treatment for 6 h did not alter global gene expression. Higher concentration of propofol exerted potential cytotoxicity via multiple cellular mechanisms. In summary, propofol treatment at commonly practiced clinical doses for 6 h did not have adverse effects on hiPSC-derived NPCs. In contrast, longer exposure and/or higher concentration of propofol treatment could decrease NPC viability and induce apoptosis.
2017-07-21 | GSE101724 | GEO
Project description:Background: Propofol is a short-acting anesthetic, which is often used for induction and maintenance of general anesthesia, sedation for mechanically ventilated adults and procedural sedation. Several side effects of propofol are known and a substantial number of patients suffer from post-operative delirium after propofol application. In this study, we analyzed the effect of propofol on the function and protein expression profile on a proteome-wide scale. Methods: We cultured human brain microvascular endothelial cells in the absence and presence of propofol and analyzed the permeability of the blood-brain barrier (BBB) by fluorescein passage and protein expression on a proteome-wide scale by mass spectrometry. Results: Propofol interfered with the function of the blood-brain barrier. This was not due to de-creased adhesion of propofol-treated human brain microvascular endothelial cells. The proteomic analysis revealed that some key pathways in these cells were disturbed, such as oxygen metabolism, DNA damage recognition and response to stress. Conclusions: Propofol has strong effects on protein expression which could explain several side effects of propofol.
2022-10-13 | PXD033856 | Pride
Project description:Anesthetic management of heart failure patients undergoing noncardiac surgery remains challenging due to cardiac suppressive properties of anesthetics. Due to varying electrophysiological properties, small and large animals are not good models for studying human myocardial anesthetic responses. Here we use hypertrophic (HCM), dilated (DCM) and healthy human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) to evaluate the cardiac suppression of propofol and etomidate. We demonstrate that propofol and etomidate act through GABAA receptors and contractile inhibition can occur without cell-cell junction. At supraphysiological dosage (100mM), we discovered that cardiac suppression induced by etomidate is reversible while propofol is not. Using transcriptome profiling, we uncover that etomidate was capable of inducing autophagy, likely through induction of cytosolic calcium. Lack of autophagy induction in propofol treated cardiomyocytes were associated with increased apoptosis. Together, we provide the robustness of using hiPSC-CMs as an in vitro cardiotoxicity platform for anesthetics. To delineate how etomidate confers cardioprotection during contraction inhibition, we performed transcriptome profiling on DCM hiPSC-CMs treated with either 10 μM propofol, 10 μM etomidate or DMSO control.
2022-08-30 | GSE212044 | GEO
Project description:The basic mechanisms of action for general anesthesia are not fully understood. We thought differences in the neural activation sites of different types of anesthetics and differences in gene expression changes in those brain regions may lead to differences in the incidence of side effects. We performed gene expression analysis using microarrays in the identified regions that have been related to the mechanisms of anesthetic action and side effects. Gene expression changes in these brain regions were determined for sevoflurane and propofol to understand the mechanisms that cause differences among anesthetics.
2021-12-22 | GSE192399 | GEO
Project description:General anesthesia is thought to suppress the immune system and negatively affect postoperative infection and the long-term prognosis of cancer. However, the mechanism underlying immunosuppression induced by general anesthetics remains unclear. In this study, we focused on propofol, which is widely used for sedation under general anesthesia and intensive care and examined its effects on the T cell function and T cell-dependent immune responses. We found that propofol suppressed T cell glycolytic metabolism, differentiation into effector T cells, and cytokine production by effector T cells. CD8 T cells activated and differentiated into effector cells in the presence of propofol in vitro showed reduced antitumor activity. Furthermore, propofol treatment suppressed the increase in the number of antigen-specific CD8 T cells during Listeria infection. In contrast, the administration of propofol improved inflammatory conditions in mouse models of inflammatory diseases, such as OVA-induced allergic airway inflammation, hapten-induced contact dermatitis, and experimental allergic encephalomyelitis. These results suggest that propofol may reduce tumor and infectious immunity by suppressing the T cell function and T cell-dependent immune responses while improving the pathogenesis and prognosis of chronic inflammatory diseases by suppressing inflammation.
| S-EPMC11336218 | biostudies-literature
Project description:Anesthetic gases elicit organ protection in patients undergoing coronary artery bypass graft (CABG) surgery. This study aimed at identifying myocardial transcriptional phenotypes and anesthetic-induced changes in gene expression to predict cardiovascular biomarkers and cardiac function after off-pump CABG. Experiment Overall Design: Patients scheduled for off-pump CABG were randomized into a group with the anesthetic gas sevoflurane (n=10) or the intravenous anesthetic propofol (n=10). Atrial samples were collected at the beginning and end of bypass surgery to determine gene expression profiles.
2008-11-22 | E-GEOD-4386 | biostudies-arrayexpress
Project description:Anesthetic method was reported to have an impact on postoperative long-term outcome in cancer patients. In this study, we will investigate the effect of different anesthetic methods on NK cell activity, cytokine response and postoperative outcome in colorectal cancer patients undergoing CRS and HIPEC. We will compare propofol-based total intravenous anesthesia (TIVA) with balanced anesthesia to determine the effect of propofol, inhalation agent, and opioid on tumor genesis, recurrence, NK cell activity, cytokine response, and postoperative outcome.
| 66979 | ecrin-mdr-crc
Project description:The goal of this observational study is to compare anesthetic modalities (intravenous propofol anesthesia with sevoflurane gas anesthesia) in patients who underwent colorectal cancer resection surgery regarding the outcome of acute kidney injury.
The main questions it aims to answer are:
* is there a difference in acute kidney injury incidence in the two anesthetic modalities?
* is there a difference in plasma creatinine between the two anesthetic modalities?
* are there any patient characteristics or intraoperative factors that effect the incidence of acute kidney injury in either anesthetic modality?
The study will analyze data from the CAN clinical trial database. (Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia, NCT01975064)
| 2751857 | ecrin-mdr-crc
Project description:Propofol has been found to be toxic to developing neurons. The goal of the current study was to nominate novel genes predicted to underly the neurotoxicity, and use these candidates for future functional pathway assessment
2017-11-14 | GSE106799 | GEO