Isoflurane attenuates pulmonary interleukin-1β and systemic tumor necrosis factor-α following mechanical ventilation in healthy mice

M. Vaneker, J. P. Santosa, L. M. Heunks, F. J. Halbertsma, D. G. Snijdelaar, J. Van Egmond, I. A. Van Den Brink, F. M. Van De Pol, J. G. Van Der Hoeven, G. J. Scheffer

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Background: Mechanical ventilation (MV) induces an inflammatory response in healthy lungs. The resulting pro-inflammatory state is a risk factor for ventilator-induced lung injury and peripheral organ dysfunction. Isoflurane is known to have protective immunological effects on different organ systems. We tested the hypothesis that the MV-induced inflammatory response in healthy lungs is reduced by isoflurane. Methods: Healthy C57BL6 mice (n=34) were mechanically ventilated (tidal volume, 8 ml-kg; positive end-expiratory pressure, 4 cmH 2O; and fraction of inspired oxygen, 0.4) for 4 h under general anesthesia using a mix of ketamine, medetomidine and atropine (KMA). Animals were divided into four groups: (1) Unventilated control group; (2) MV group using KMA anesthesia; (3) MV group using KMA with 0.25 MAC isoflurane; (4) MV group using KMA with 0.75 MAC isoflurane. Cytokine levels were measured in lung homogenate and plasma. Leukocytes were counted in lung tissue. Results: Lung homogenates: MV increased pro-inflammatory cytokines. In mice receiving KMA+ isoflurane 0.75 MAC, no significant increase in interleukin (IL)-1β was found compared with non-ventilated control mice. Plasma: MV induced a systemic pro-inflammatory response. In mice anesthetized with KMA+ isoflurane (both 0.25 and 0.75 MAC), no significant increase in tumor necrosis factor (TNF)-α was found compared with non-ventilated control mice. Conclusions: The present study is the first to show that isoflurane attenuates the pulmonary IL-1β and systemic TNF-α response following MV in healthy mice.

Original languageEnglish
Pages (from-to)742-748
Number of pages7
JournalActa Anaesthesiologica Scandinavica
Issue number6
Publication statusPublished - 1 Jul 2009

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