Anti‐Inflammatory and Antioxidative Effects of Propofol on Lipopolysaccharide‐Activated Macrophages

Abstract

Sepsis is a serious and life-threatening syndrome that often occurs in intensive care unit (ICU) patients. During sepsis, inflammatory cytokines and nitric oxide (NO) can be overproduced, causing tissue and cell injury. Propofol is an intravenous agent used for sedation of ICU patients. Our previous study showed that propofol has immunosuppressive effects on macrophage functions. This study was designed to evaluate the anti-inflammatory and antioxidative effects of propofol on the biosyntheses of tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), IL-6, and NO in lipopolysaccharide (LPS)- activated macrophages. Exposure to a therapeutic concentration of propofol (50 microM), LPS (1 ng/mL), or a combination of these two drugs for 1, 6, and 24 h was not cytotoxic to the macrophages. ELISA revealed that LPS increased macrophage TNF-alpha, IL-1beta, and IL-6 protein levels in a time-dependent manner, whereas propofol significantly reduced the levels of LPS-enhanced TNF-alpha, IL-1beta, and IL-6 proteins. Data from RT-PCR showed that LPS induced TNF-alpha, IL-1beta, and IL-6 mRNA, but propofol inhibited these effects. LPS also increased NO production and inducible nitric oxide synthase (iNOS) expression in macrophages. Exposure of macrophages to propofol significantly inhibited the LPS-induced NO biosynthesis. The present study shows that propofol, at a therapeutic concentration, has anti-inflammatory and antioxidative effects on the biosyntheses of TNF-alpha, IL-1beta, IL-6, and NO in LPS-activated macro-phages and that the suppressive effects are exerted at the pretranslational level.

Propofol inhibits pressure-stimulated macrophage phagocytosis via the GABAA receptor and dysregulation of p130cas phosphorylation

“…Propofol has been proposed to decrease lipid peroxidation and activate the immune system (13). Conversely, propofol has also been reported to inhibit immune cell functions, such as LPS-induced cytokine release and the oxidative stress response (10). Propofol also attenuates Kupffer cell activation and LPS-induced hepatocellular damage (57,58).…”

“…Propofol is also known to alter the functions of immunocompetent cells, such as neutrophils, monocytes, and macrophages (10,11,36). Propofol decreases proinflammatory cytokine production and inducible nitric oxide synthase expression in LPS-stimulated mouse macrophage Raw 264.7 cells (10,11) and increases bacterial accumulation in lung and liver after venous infusion compared with the effects of saline infusion (26). Propofol binds to the ␤ 2 -subunit of the GABA A receptor (4,16), which regulates Cl Ϫ channels (32).…”

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

“…Previous studies indicated that the well-known anti-oxidant properties of propofol might be related to its chemical structure, which is similar to that of phenol-based scavengers such as tocopherols. 1,9,[42][43][44] Indeed, a-tocopherol is reported to have a strong anti-oxidizing effect. 42 Similarly, propofol's inhibitory effect on COX might be ascribable to its structural similarity to c-tocopherol.…”

Effects of intra‐operative maintenance of general anaesthesia with propofol on postoperative pain outcomes – a systematic review and meta‐analysis

“…Propofol has been proven to inhibit pro-inflammatory cytokines induced by lipopolysaccharide, including IL-b, IL-6 and TNF-a. These cytokines play important roles in pain signalling [3]. Propofol scavenges free radicals with a fast and stable kinetic feature in vitro, which is useful and important for understanding its anti-oxidant properties, and may also play a role in dynamic protection in the body [4].…”