Effects of sevoflurane, propofol, remifentanil, and fentanyl on the endothelial proinflammatory response: an in vitro exploratory study

The vascular endothelium is known to modulate the inflammatory response during surgery. Sevoflurane has been shown to protect against tumor necrosis factor alpha (TNF-α)-induced endothelial dysfunction, but the effects of other anesthetics or combinations with opioids on endothelial response are unclear.

In this in vitro study, we stimulated human umbilical vein endothelial cells with TNF-α (10 ng·mL^-1) in triplicate in three independent experiments and treated them with sevoflurane (0.8%, 2.0%, and 4.0%), propofol (2, 5, and 10 μg·mL^-1), remifentanil (2, 5, and 10 ng·mL^-1) and fentanyl (0.5, 1.5, and 5 ng·mL^-1) individually and in combinations. We evaluated the expression levels of endothelial adhesion molecules and proinflammatory cytokines using reverse transcription quantitative real-time polymerase chain reaction, Western blotting, and the enzyme-linked immunosorbent assay.

Only sevoflurane significantly diminished the messenger ribonucleic acid (mRNA) and protein expression of adhesion molecules in the presence of TNF-α (E-selectin [sevoflurane 0.8%, P < 0.001; 2%, P = 0.03; 4%, P = 0.004], vascular cell adhesion molecule 1 [sevoflurane 0.8%, P < 0.001; 2%, P = 0.002; 4%, P < 0.001], and intercellular adhesion molecule 1 [sevoflurane 0.8%, P = 0.002; 2%, P = 0.007; 4%, P < 0.001]). Additionally, mRNA and protein expression of the proinflammatory cytokines interleukin [IL]-6 and IL-8 decreased after exposure to sevoflurane alone for (IL-6 mRNA: sevoflurane 0.8%, P = 0.004; 4%, P < 0.001; IL-8 mRNA: sevoflurane 4%, P = 0.02; IL-6 protein: sevoflurane 0.8%, P < 0.001; 2%, P = 0.003; 4%, P < 0.001; IL-8 protein: sevoflurane 0.8%, P = 0.03; 2%, P < 0.001; 4%, P = 0.008]). The addition of opioids did not change the expression in either of the adhesion molecules or inflammatory cytokines.

In this exploratory study, sevoflurane inhibited endothelial adhesion molecules and proinflammatory response in vitro, whereas propofol, remifentanil, or fentanyl did not possess the same effect. While the effects in vivo are unknown, these findings might highlight the potential impact of anesthetic choice on modulating the inflammatory response of endothelial cells.