• J M Fuentes, E J Hanly, A R Aurora, A De Maio, S P Shih, M R Marohn, and M A Talamini.
• Department of Surgery, The Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 665, Baltimore, MD, 21287-4665, USA.
• Surg Endosc. 2006 Aug 1; 20 (8): 1225-32.

BackgroundLaparoscopic surgery preserves the immune system and has anti-inflammatory properties. CO2 pneumoperitoneum attenuates lipopolysaccharide (LPS)-induced cytokine production and increases survival. We tested the hypothesis that CO2 pneumoperitoneum mediates its immunomodulatory properties via stimulation of the cholinergic pathway.MethodsIn the first experiment, rats (n = 68) received atropine 1 mg/kg or saline injection 10 min prior to LPS injection and were randomization into four 30-min treatment subgroups: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. In a second experiment, rats (n = 40) received atropine 2 mg/kg or saline 10 min prior to randomization into the same four subgroups described previously. In a third experiment, rats (n = 96) received atropine 2 mg/kg or saline 10 min prior to randomization into eight 30-min treatment subgroups followed by LPS injection: LPS only control; anesthesia control; and CO2 or helium pneumoperitoneum at 4, 8, and 12 mmHg. In a fourth experiment, rats (n = 58) were subjected to bilateral subdiaphragmatic truncal vagotomy or sham operation. Two weeks postoperatively, animals were randomized into four 30-min treatment subgroups followed by LPS injection: LPS only control, anesthesia control, CO2 pneumoperitoneum, and helium pneumoperitoneum. Blood samples were collected from all animals 1.5 h after LPS injection, and cytokine levels were determined by enzyme-linked immunosorbent assay.ResultsSerum tumor necrosis factor-alpha (TNF-alpha) levels were consistently suppressed among the saline-CO2 pneumoperitoneum groups compared to saline-LPS only control groups (p < 0.05 for all four experiments). All chemically vagotomized animals had significantly reduced TNF-alpha levels compared to their saline-treated counterparts (p < 0.05 for all), except among the CO2 pneumoperitoneum-treated animals. Increasing insufflation pressure with helium eliminated differences (p < 0.05) in TNF-alpha production between saline- and atropine-treated groups but had no effect among CO2 pneumoperitoneum-treated animals. Finally, vagotomy (whether chemical or surgical) independently decreased LPS-stimulated TNF-alpha production in all four experiments.ConclusionCO2 pneumoperitoneum modulates the immune system independent of the vagus nerve and the cholinergic pathway.

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