Isoflurane attenuates pulmonary interleukin-1beta and systemic tumor necrosis factor-alpha following mechanical ventilation in healthy mice.
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(2)O; 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)-1beta 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)-alpha was found compared with non-ventilated control mice.


CONCLUSIONS
The present study is the first to show that isoflurane attenuates the pulmonary IL-1beta and systemic TNF-alpha response following MV in healthy mice.
Vaneker
M
M
Departments of Anesthesiology and Intensive Care, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. m.vaneker@anes.umcn.nl
Santosa
J P
JP
Heunks
L M
LM
Halbertsma
F J
FJ
Snijdelaar
D G
DG
VAN Egmond
J
J
VAN DEN Brink
I A
IA
VAN DE Pol
F M
FM
VAN DER Hoeven
J G
JG
Scheffer
G J
GJ
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism*; D007530:Isoflurane / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology; D007958:Leukocyte Count; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D020926:Medetomidine / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011014:Pneumonia / Q000473:pathology; D012121:Respiration, Artificial; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D006993:Hypnotics and Sedatives; D053583:Interleukin-1beta; D018727:Muscarinic Antagonists; D014409:Tumor Necrosis Factor-alpha; D007649:Ketamine; D001285:Atropine; D007530:Isoflurane; D020926:Medetomidine