The beta-adrenoceptor antagonist propranolol counteracts anti-inflammatory effects of isoflurane in rat endotoxemia.
BACKGROUND
Recent studies suggest that volatile anaesthetics have anti-inflammatory and preconditioning properties and that beta-adrenoceptors are involved in the signalling pathways for these effects. Concurrently, the blockade of beta-adrenoceptors has been shown to augment the release of inflammatory mediators in response to pro-inflammatory stimuli. We therefore aimed to investigate whether the beta-adrenoceptor antagonist propranolol might modulate the anti-inflammatory effects of isoflurane on the systemic and pulmonary release of pro-inflammatory cytokines in endotoxemic rats.


METHODS
Forty anaesthetized and ventilated Sprague-Dawley rats were randomly treated as follows. Lipopolysaccharide (LPS) only (n = 8), endotoxemia with LPS [5 mg/kg, intravenously (i.v.)]. LPS-isoflurane (n = 8): endotoxemia and continuous inhalation of 1 minimum alveolar concentration (MAC) of isoflurane. LPS-isoflurane-propranolol (n = 8): administration of propranolol (3 mg/kg) before continuous inhalation of isoflurane and induction of endotoxemia. LPS-propranolol (n = 8): administration of propranolol (3 mg/kg) before endotoxemia without inhalation of isoflurane. Sham (n = 8): control-group only with surgical preparation. After 4 h of endotoxemia, levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-10 (IL-10) in plasma and bronchoalveolar fluid (BALF) were analysed. Release of nitric oxide (NO) and amount of inducible nitric oxide synthase (iNOS) protein in alveolar macrophages was measured by Griess assay or determined by Western Blotting, respectively.


RESULTS
Inhalation of isoflurane reduced the release of TNF-alpha (P < 0.05) and IL-1beta (P < 0.05) in plasma and IL-1beta (P < 0.05) in BALF. Co-administration of propranolol significantly inhibited these effects. During inhalation of isoflurane, the increased release of NO and iNOS protein from alveolar macrophages was also completely inhibited by propranolol.


CONCLUSIONS
Our results indicate for the first time, that blockade of beta-adrenoceptors counteracts the anti-inflammatory effects of isoflurane in endotoxemic rats.
Boost
K A
KA
Department of Anaesthesiology, Intensive Care and Pain Therapy, University Hospital of Johann Wolfgang Goethe-University Frankfurt am Main, Germany. k.boost@med.uni-frankfurt.de
Flondor
M
M
Hofstetter
C
C
Platacis
I
I
Stegewerth
K
K
Hoegl
S
S
Nguyen
T
T
Muhl
H
H
Zwissler
B
B
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000037:antagonists & inhibitors*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D019446:Endotoxemia / Q000378:metabolism / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006339:Heart Rate / Q000187:drug effects; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007530:Isoflurane / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D018685:Anesthetics, Inhalation; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D011433:Propranolol; D007530:Isoflurane; D052247:Nitric Oxide Synthase Type II