Intraoperative prostaglandin E1 improves antimicrobial and inflammatory responses in alveolar immune cells

摘要

ObjectiveAnesthesia and surgery decrease antimicrobial and increase proinflammatory functions of alveolar immune cells. Thus, anti-inflammatory agents that do not further suppress antimicrobial functions are required. We tested the hypothesis that intraoperative prostaglandin E1 (PGE1) suppresses proinflammatory responses and prevents the reduction in antimicrobial responses of alveolar immune cells.DesignProspective, randomized, controlled, double-blind study.SettingUniversity hospital.PatientsA total of 40 patients undergoing elective orthopedic surgery under propofol/fentanyl anesthesia.InterventionIn double-blind fashion, the patients received PGE1 from the beginning to the end of surgery (PGE1 group, n equals; 20) or nothing (control group, n equals; 20).Methods and Main ResultsAlveolar immune cells were harvested by bronchoalveolar lavage immediately after induction of anesthesia; 2, 4, and 6 hrs after induction of anesthesia; and at the end of surgery. We measured opsonized and nonopsonized phagocytosis. Microbicidal activity was evaluated to directly killListeria monocytogenesin alveolar macrophages. Finally, we determined the expression of proinflammatory cytokines including interleukin (IL)-1bgr;, IL-8, interferon-ggr;, and tumor necrosis factor-agr;, and that of anti-inflammatory cytokines (IL-4 and IL-10) by semiquantitative polymerase chain reaction. Nonopsonized and opsonized phagocytosis and microbicidal activity of alveolar macrophages decreased and the expression of genes for all pro- and anti-inflammatory cytokines increased significantly over time in both groups. Starting 2ndash;4 hrs after induction of anesthesia, the increases in gene expression of proinflammatory cytokines were 1.5ndash;3 times smaller in the PGE1 than in the control group. Starting 6 hrs after anesthesia, the increase in gene expression of IL-10 was 1.5ndash;3 times greater in the PGE1 than in the control group. Intraoperative decreases in phagocytic and microbial activities were the same in the two groups.ConclusionIntraoperative PGE1 not only suppressed proinflammatory responses, but also protected antimicrobial functions of alveolar macrophages, possibly because PGE1 is mostly inactivated in the pulmonary intravascular space. Our results suggest that intraoperative PGE1 protects the pulmonary immune defense in alveolar immune cells.