Volatile Anesthetics Augment Expression of Proinflammatory Cytokines in Rat Alveolar Macrophages during Mechanical Ventilation

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Abstract

Background

Previous studies indicate that anesthesia and surgery induce an inflammatory reaction in alveolar macrophages. However, they failed to independently evaluate the relative contributions of factors including mechanical ventilation, general anesthesia, and surgical stress. Therefore, the authors tested the hypothesis that inflammatory reactions at the cellular level in alveolar macrophages are induced within 2 h of inhalation of volatile anesthetics under mechanical ventilation.

Methods

After administration of pentobarbital, rats were allocated to the nonventilated control or spontaneous or mechanical ventilation (n = 15/group) for 2 h at a fraction of inspired oxygen (FIO(2)) of 0.21. In a separate series of experiments, rats were mechanically ventilated without volatile anesthesia, or during exposure to halothane, enflurane, isoflurane, or sevoflurane (n = 15/group). Pulmonary lavage was performed, and RNA was extracted from harvested cells. The mRNA for the proinflammatory cytokines interleukin (IL)-1 [Greek small letter alpha], IL-1 [Greek small letter beta], IL-6, macrophage inflammatory protein-2 (MIP-2), interferon gamma (IFN-[Greek small letter gamma]), and tumor necrosis factor alpha (TNF-[Greek small letter alpha]) were measured by semiquantitative reverse transcription-polymerase chain reaction using [Greek small letter beta]-actin as an internal standard. Pulmonary lavage concentrations of these cytokines were measured by enzyme-linked immunoassay.

Results

The lavage cell count and cytology were similar in each series of the experiment. Gene expression of MIP-2 and TNF-[Greek small letter alpha] was greater during mechanical than spontaneous ventilation and nonventilation control. However, the concentrations of cytokines except MIP-2 and TNF-[Greek small letter alpha] were less than detection levels. During exposure to volatile anesthetics, gene expression for IL-1 [Greek small letter beta], MIP-2, IFN-[Greek small letter gamma], and TNF-[Greek small letter alpha] all increased significantly compared with mechanical ventilation alone. Significant increases in lavage concentrations of MIP-2 and TNF-[Greek small letter alpha] were also observed.

Conclusions

Gene expression of proinflammatory cytokines increase after inhalation of volatile anesthetics under mechanical ventilation. These data indicate that inhalation of volatile anesthetics under mechanical ventilation induces an inflammatory response at the transcriptional level within 2 h.

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