Propofol inhibits cyclo-oxygenase activity in human monocytic THP-1 cells

Abstract

Purpose: Monocytes/macrophages are key players in innate and adaptive immunity. Upon stimulation, they secrete prostanoids, which are produced by cyclooxygenase from arachidonic acid. Prostanoids influence inflammation and immune responses. We investigated the effect of propofol on prostaglandin E 2 and thromboxane B2 production by the human monocytic cell line THP-1. Methods: The THP-1 cells were cultured with lipopolysaccharide (1 μg ml-1) in the presence of clinically relevant sedative/anesthetic concentrations of propofol (0-30 μM) for 18 h, and the concentration of prostaglandin E2 and thromboxane B2 in culture supernatants was measured using an enzyme immunoassay. Intracellular cyclooxygenase protein expression was measured by flow cytometry. Cyclooxygenase activity was assessed by measuring production of prostaglandin E2 and thromboxane B2 by THP-1 cells after arachidonic acid (10 μM) substrate provision. Results: Propofol decreased the production of prostaglandin E2 (75.4 ± 6.4 pg ml-1 at 0 μM vs. 28.5 ± 11.2 pg ml-1 at 30 μM; P < 0.001) and thromboxane B2 (282.4 ± 79.2 pg ml-1 at 0 μM vs. 40.4 ± 21.7 pg ml-1 at 30 μM; P < 0.001). The inhibition was not due to the decreased cyclooxygenase protein expression because intracellular staining of this enzyme was not affected by propofol. After arachidonic acid provision, prostaglandin E2 and thromboxane B2 production from activated THP-1 cells was significantly (P < 0.001) decreased with propofol, indicating direct suppression of cyclooxygenase activity with propofol. Conclusions: Propofol may modulate inflammation via the suppression of cyclooxygenase activity. Through the inhibition of prostanoid production, propofol may enhance immune responses. © 2009 Canadian Anesthesiologists' Society.