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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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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