SummaryThere are two major subpopulations of peripheral helper T lymphocytes: T helper 1 (Th1) and T helper 2 (Th2) cells. Surgical stress increases the number of Th2 cells, and decreases that of Th1 cells, resulting in a decrease in the Th1 ⁄ Th2 ratio, and, consequently, in suppressed cellmediated immunity. Since anaesthesia can suppress the stress response to surgery, it may inhibit the decrease in the Th1 ⁄ Th2 ratio. Using flow cytometry, we studied whether propofol anaesthesia (n = 9) or isoflurane anaesthesia (n = 9) had more effect on the decrease in the Th1 ⁄ Th2 ratio after surgery in patients undergoing craniotomy. The Th1 ⁄ Th2 ratio decreased significantly after isoflurane anaesthesia (p = 0.011), while it did not change after propofol anaesthesia. The ratio was significantly lower with isoflurane than propofol (p = 0.009). Propofol anaesthesia attenuated the surgical stress-induced adverse immune response better than isoflurane anaesthesia.

Propofol and midazolam are the most widely used sedatives in the intensive care setting after surgery. We studied whether these sedatives had any antitumor immunity effects in mice. Mice were given intraperitoneal injections of propofol or midazolam and subcutaneous inoculation of tumor cells (EL4). Then, spleen cells were collected and the in vitro activity of cytotoxic T lymphocytes (CTL) was measured using flow cytometry. The in vitro activity of CTL against EL4 was significantly greater after propofol injection compared with its vehicle (Intralipid) or saline. Midazolam had no effect on CTL activity. We also studied whether tumor growth in vivo was affected by the administration of propofol. Tumor growth was significantly suppressed in mice that were given propofol, compared with tumor growth in mice given saline. Therefore, it is concluded that propofol may have a beneficial effect on antitumor immunity in mice.

The intravenous anesthetic propofol has a number of well-known nonanesthetic effects, including anti-oxidation and anti-emesis. Another interesting nonanesthetic effect of propofol may be its cyclooxygenase (COX)-inhibiting activity. This activity may have important clinical implications, as propofol could have antitumor properties through COX inhibition. Propofol could counteract the activity of COX, which elicits, via its major product prostaglandin E(2), (1) tumor growth stimulation, (2) increased tumor survival, (3) enhanced tumor invasiveness, (4) stimulation of new vessel formation, and (5) tumor evasion of host immune surveillance through suppression of immune cell functions. Indeed, accumulated evidence indicates that propofol suppresses the proliferation, motility, and invasiveness of tumors in vitro and in vivo. Therefore, propofol could be a particularly suitable anesthetic for use during the perioperative period for cancer surgery. However, whether the COX-inhibiting activity of propofol is related to the reported antitumor properties of propofol is not known. Definitive evidence remains to be provided.

We studied the effect of propofol and midazolam on gastric emptying and gastrointestinal transit in mice. Ten minutes after intraperitoneal injection of propofol or midazolam, 0.2 mL of saline containing fluorescent microbeads was infused into the stomach. Thirty minutes later, the gastrointestinal tract was excised, and gastric emptying and gastrointestinal transit were calculated by measuring the quantity of fluorescent microbeads in the gastrointestinal tract by using a flow cytometer. At a dose that produced a light level of sedation (mice righted themselves within 2 s), both drugs significantly, but weakly, inhibited gastric emptying to a similar degree (propofol: P < 0.001 versus control value; 95% confidence interval [CI] for difference, 4.9%-20.2%; midazolam: P < 0.001 versus control value; 95% CI for difference, 7.8%-14.7%). Midazolam, but not propofol, delayed gastrointestinal transit (P < 0.001). At a larger dose that produced a deeper level of sedation (absence of righting reflex >10 s), both drugs significantly inhibited gastric emptying (propofol: P < 0.001; 95% CI for difference, 31.4%-61.2%; midazolam: P < 0.001; 95% CI for difference, 30.8%-61.1%) and gastrointestinal transit (P < 0.001 for both drugs).

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 B 2 production by the human monocytic cell line THP-1. Methods The THP-1 cells were cultured with lipopolysaccharide (1 lg ml -1 ) in the presence of clinically relevant sedative/anesthetic concentrations of propofol (0-30 lM) for 18 h, and the concentration of prostaglandin E 2 and thromboxane B 2 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 E 2 and thromboxane B 2 by THP-1 cells after arachidonic acid (10 lM) substrate provision. Results Propofol decreased the production of prostaglandin E 2 (75.4 ± 6.4 pg ml -1 at 0 lM vs. 28.5 ± 11.2 pg ml -1 at 30 lM; P \ 0.001) and thromboxane B 2 (282.4 ± 79.2 pg ml -1 at 0 lM vs. 40.4 ± 21.7 pg ml -1at 30 lM; 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 E 2 and thromboxane B 2 production from activated THP-1 cells was significantly (P \ 0.001) decreased with propofol, indicating direct suppression of cyclooxygenase activity with propofol.