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.

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.

Prostaglandin E(2) secreted from monocytes/macrophages plays important roles in immunity and in inflammation. Currently, propofol, an intravenous anesthetic, is the most widely used drug for the anesthesia and sedation of patients, including those who are vulnerable to infection and/or immunosuppression. Here we report that propofol suppressed prostaglandin E(2) production in lipopolysaccharide-activated human peripheral monocytes. The suppressive effects of propofol were ascribed to its inhibition of cyclooxygenase-2 activity rather than to effects on cyclooxygenase protein expression or substrate availability. Thus, propofol seems to have a prominent effect on immunity and inflammation.

Dexmedetomidine, a selective alpha2 adrenergic receptor agonist, is a drug often used for sedation. Despite the high prevalence of sedating patients with tumors in intensive care settings, little is known about the effect of sedative drugs on tumor growth. We studied the effect of dexmedetomidine on antitumor immunity in mice. Subhypnotic doses of dexmedetomidine decreased interleukin (IL)-12 production from thioglycollate-induced macrophages. The treatment also decreased the ratio of the helper T lymphocytes subsets, Th1 to Th2 (Th1/Th2), in the spleen. Following subcutaneous inoculation of EL4 T-cell lymphoma cells, dexmedetomidine further decreased the splenic Th1/Th2 ratio and activity of EL4-specific cytotoxic T lymphocytes (CTLs). Finally, treatment with dexmedetomidine accelerated EL4 growth in mice. These data show that treatment of mice with subhypnotic doses of dexmedetomidine down-regulates antitumor immunity, possibly through the decreased production of IL-12 from antigen presenting cells, resulting in a Th2 shift and decreased CTL activity against EL4 in mice.

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