Effects of propofol and its formulation components on macrophages and neutrophils in obese and lean animals

Abstract

We hypothesized whether propofol or active propofol component (2,6‐diisopropylphenol [DIPPH] and lipid excipient [LIP‐EXC]) separately may alter inflammatory mediators expressed by macrophages and neutrophils in lean and obese rats. Male Wistar rats ( n = 10) were randomly assigned to receive a standard (lean) or obesity‐inducing diet (obese) for 12 weeks. Animals were euthanized, and alveolar macrophages and neutrophils from lean and obese animals were exposed to propofol (50 µM), active propofol component (50 µM, 2,6‐DIPPH), and lipid excipient (soybean oil, purified egg phospholipid, and glycerol) for 1 h. The primary outcome was IL‐6 expression after propofol and its components exposure by alveolar macrophages extracted from bronchoalveolar lavage fluid. The secondary outcomes were the production of mediators released by macrophages from adipose tissue, and neutrophils from lung and adipose tissues, and neutrophil migration. IL‐6 increased after the exposure to both propofol (median [interquartile range] 4.14[1.95–5.20]; p = .04) and its active component (2,6‐DIPPH) (4.09[1.67–5.91]; p = .04) in alveolar macrophages from obese animals. However, only 2,6‐DIPPH increased IL‐10 expression (7.59[6.28–12.95]; p = .001) in adipose tissue‐derived macrophages. Additionally, 2,6‐DIPPH increased C‐X‐C chemokine receptor 2 and 4 (CXCR2 and CXCR4, respectively) in lung (10.08[8.23–29.01]; p = .02; 1.55[1.49–3.43]; p = .02) and adipose tissues (8.78[4.15–11.57]; p = .03; 2.86[2.17–3.71]; p = .01), as well as improved lung‐derived neutrophil migration (28.00[−3.42 to 45.07]; p = .001). In obesity, the active component of propofol affected both the M1 and M2 markers as well as neutrophils in both alveolar and adipose tissue cells, suggesting that lipid excipient may hinder the effects of active propofol.

Comparison between sevoflurane and propofol on immunomodulation in an in vitro model of sepsis

“…BALF was centrifuged (300×g, 5 min) and the cell pellet was resuspended in 2 mL od 1× PBS. Blood and BALF cells were slowly transferred to a tube containing Ficoll-Paque (Sigma, St Louis, MO, United States), then centrifuged (400×g at 20°C) for 30 min to isolate mononuclear and polymorphonuclear cells over the density gradient created by centrifugation (25)(26)(27)(28)(29). Mononuclear and polymorphonuclear cells were then treated with red blood cell lysis buffer (Sigma) for 5 min, washed twice with 1× PBS, and centrifuged (400×g at 20°C) for 5 min.…”

Effects of propofol on macrophage activation and function in diseases

“…An animal model demonstrated that propofol and lipid excipients had different immunomodulatory effects in obesity, and the active components in propofol increased the expression of IL-10 and M2 phenotypes in macrophages from adipose tissue. Propofol and its active components increased IL-6 expression in obese animals ( Heil et al, 2021 ). With the increase in the obese population, understanding the immune regulation of propofol on macrophages in obese patients will be helpful for proposing an anesthesia management program.…”

“…Increased expression of glucose transporter 1 (GLUT1) on the surface of macrophages in adipose tissue suggests that GLUT1 is associated with inflammation in vivo . Propofol also regulated the metabolism of macrophages, which regulates the metabolism of activated macrophages by inhibiting the overexpression of ROS and decreasing the expression of GLUT1 ( Heil et al, 2021 ). Arteriosclerosis is a type of inflammatory vascular disease, and the regulation of propofol has a positive effect on arteriosclerosis formation.…”