Effects of propofol on the leukocyte nitric oxide pathway: in vitro and ex vivo studies in surgical patients

Abstract

This study was designed to evaluate the mechanism by which propofol modifies leukocyte production of nitric oxide (NO) in humans. In vitro experiments used whole blood from healthy volunteers (n = 10 samples/experiment). Ex vivo experiments studied the effects of an intravenous dose of 2.5 mg propofol per kilogram body weight followed by intravenous infusion of 4 mg kg(-1) h(-1) in surgical patients in ASA class I or II (n = 20). In whole blood, neutrophils and plasma, we measured NO production and the activities of the enzymes nitric oxide synthase [inducible (iNOS) and constitutive (cNOS)] and cyclooxygenase [constitutive (COX-1) and inducible (COX-2)]. Concentrations of interleukins (IL-1beta, IL-6, and IL-10) and tumor necrosis factor-alpha (TNFalpha) were measured in plasma. In blood from healthy donors, propofol increased NO production and cNOS activity. The concentration of propofol that increased NO production by 50% (EC(50)) was 23.5 microM, and the EC(50) of propofol for cNOS was 18.6 microM. In blood from surgical patients, propofol increased NO production by 52% and cNOS activity by 57%. Propofol inhibited iNOS activity in vitro; the concentration that reduced activity by 50% (IC(50)) was 19.9 microM. In surgical patients propofol inhibited iNOS activity by 53%. COX-1 and COX-2 activities were inhibited in vitro (IC(50) 32.6 and 187 microM, respectively) and in surgical patients (53 and 81% inhibition, respectively). Plasma concentrations of IL-1beta, IL-6, and TNFalpha were significantly reduced in surgical patients (32, 23, and 21% inhibition, respectively). None of these parameters were modified in a group of patients (n = 10) anesthetized with sevoflurane. We conclude that propofol stimulated constitutive NO production and inhibited inducible NO production, possibly by curtailing the stimulation of iNOS by inflammatory mediators in surgical patients.

Effect of dexmedetomidine, midazolam, and propofol on lipopolysaccharide‑stimulated dendritic cells

“…The numbers of reports about the effects of propofol on inflammation outnumber those of the other two sedatives (29). Though the inhibit effect of propofol on cytokine were similar seen in many previous study, our study shows that propofol could enhanced LPS-induced COX2, that may be because of the difference cells.…”

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

“…1,2,7-11 Prostanoids, including the prostaglandins and thromboxanes, are also produced by monocytes-macrophages, 6,8,[12][13][14] but the effect of propofol on the production of prostanoids by these cells is not well documented.…”

Influence of Propofol, Isoflurane and Enflurance on Levels of Serum Interleukin-8 and Interleukin-10 in Cancer Patients

“…Multiple studies found that anesthetic agents had significant influence on serum cytokines in patients who underwent surgeries (Dermitzaki et al, 2009;Reikerås et al, 2010). Propofol, as one of the anesthetic agents commonly used in clinic, has favorable sedation, anti-inflammatory responses and anti-oxidation characteristics (Cavalca et al, 2008;Gonzalez-Correa et al, 2008). A report revealed that during septicopyemia, propofol could effectively suppress the release of proinflammatory cytokines TNF-α, IL-6 and IL-8 and alleviate the lung infiltration of neutrophils and acidosis (Taniguchi et al, 2002), which was predicated to be closely associated with the action of propofol on the calcium ion (Ca+) pathway in cell membrane due to the important role of Ca+ pathway played in the cytokine secretion process.…”