Application of gene therapy to acute lung injury

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(1) human research : We harvested alveolar macrophages by bronchoalveolar lavage over time. The fraction of aggregated macrophages was determined. We then measured phagocytosis and microbicidal activity. We also exploited the power of the polymerase chain reaction (PCR) to amplify mRNAs of pro-inflammatory cytokines from AMs Phagocytic and microbicidal activity progressively decreased over time, with the decrease being greater during isoflurane than propofol anesthesia. Gene expression in IL-1, IL-8, IFNィイD2γィエD2, TNFィイD2αィエD2 increased over time. The increases in IL-8 and IFNィイD2γィエD2 were greater in isoflurane than in propofol anesthesia. We report progressive impairment of pulmonary immunologic function during anesthesia and surgery. Our data suggest that pulmonary defenses are modulated by the type of anesthesia, as well as the duration of anesthesia and surgery.(2) Animal study : Rats were mechanically ventilated with halothane, enflurane, isoflurane, or sevoflurane. After whole pulmonary lavage, we examined gene expression of the pro-inflammatory cytokines. Gene expression for IL-1, MIP-2, IFNィイD2γィエD2, and TNFィイD2αィエD2 all increased significantly compared with mechanical ventilation alone. These data indicate that inhalation of volatile anesthetics under mechanical ventilation induces an inflammatory response.