Effects of propofol on macrophage activation and function in diseases

Abstract

Macrophages work with monocytes and dendritic cells to form a monocyte immune system, which constitutes a powerful cornerstone of the immune system with their powerful antigen presentation and phagocytosis. Macrophages play an essential role in infection, inflammation, tumors and other pathological conditions, but these cells also have non-immune functions, such as regulating lipid metabolism and maintaining homeostasis. Propofol is a commonly used intravenous anesthetic in the clinic. Propofol has sedative, hypnotic, anti-inflammatory and anti-oxidation effects, and it participates in the body’s immunity. The regulation of propofol on immune cells, especially macrophages, has a profound effect on the occurrence and development of human diseases. We summarized the effects of propofol on macrophage migration, recruitment, differentiation, polarization, and pyroptosis, and the regulation of these propofol-regulated macrophage functions in inflammation, infection, tumor, and organ reperfusion injury. The influence of propofol on pathology and prognosis via macrophage regulation is also discussed. A better understanding of the effects of propofol on macrophage activation and function in human diseases will provide a new strategy for the application of clinical narcotic drugs and the treatment of diseases.

Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia

“…The same lack of significant differences was reported between sedation with propofol and dexmedetomidine in ICUs [92]. What is interesting is the fact that these effects are not mediated in humans by GABA A receptors, which are not elicited on neutrophils' surfaces but via other mechanisms, like the inhibition of ROS production, p44/42 mitogen-activated protein kinase phosphorylation, and mitochondrial membrane potential [81,83,93,94]. Since most of these studies have been performed in animals, there is a lack of human studies where confounding factors may interfere, especially studies in critically ill patients, so prospective RCTs in critically ill patients for the potential effects of propofol sedation are mandatory.…”

“…Propofol acts on GABA A receptors, allowing Cl − ions to enter the cells [81,82]. GABA is one of the most important neurotransmitters in the central nervous systems [83], and GABA A (and B) receptors are widely distributed in neutrophils, monocytes, and macrophages, probably mediating the effect of propofol in immune cells [84]. In higher concentrations, propofol directly opens chloride channels and blocks glutamate release via the inhibition of certain sodium channels [81,85].…”

“…In clinically relevant concentrations, older studies reported that propofol inhibited phagocytosis and the killing of E.coli and Staphylococcus aureus [87], while others did not find this effect [88]. More recent publications highlighted propofol's effects such as regulating macrophage and neutrophil phagocytosis, pyroptosis, the production of proinflammatory cytokines (especially IL-6), and the inhibition of macrophage migration and recruitment [83,89]. Taking into consideration the effect of propofol on bacterial killing, we may expect an increase in the incidence of infections in ICUs where propofol is used for sedating critical patients for long periods of time.…”

Propofol improves survival in a murine model of sepsis via inhibiting Rab5a-mediated intracellular trafficking of TLR4

“…The cells were cultured at 37 °C in 5% CO 2 for 7 days to differentiate into macrophages before further experiments. BMDMs were treated with LPS (1 μg/ml) (L3012, sigma-Aldrich, CA, USA), and propofol (50 μm) (D126608, sigma-Aldrich, CA, USA) were added 30 min before LPS treated according to previous research [ 19 ].…”

“…In the sham group, mice underwent the same procedure, but without the cecal ligation or puncture. In the propofol-treated group, mice were pretreated with 50 mg/kg propofol (dissolved in the fat emulsion) intraperitoneally 30 min before CLP according to previous research [ 19 , 22 ]. Imipenem (a carbapenem antibiotic with a broader antimicrobial spectrum) was administered subcutaneously at a dose of 0.5 mg/d after CLP [ 23 ].…”