TY - JOUR
T1 - Anesthesia-specific protection from endotoxic shock is not mediated through the vagus nerve
AU - Fuentes, Joseph M.
AU - Hanly, Eric J.
AU - Aurora, Alexander R.
AU - De Maio, Antonio
AU - Talamini, Mark A.
N1 - Funding Information:
Supported by grant R01-GM062899-02 from the National Institutes of Health.
PY - 2005/10
Y1 - 2005/10
N2 - Background. We have shown recently that volatile anesthetics significantly decrease inflammatory cytokine production and dramatically increase survival among rodents challenged with lipopolysaccharide (LPS). Because acetylcholine's interaction with nicotine receptors on tissue macrophages during vagus nerve stimulation has been implicated in the modulation of LPS-stimulated tumor necrosis factor alpha (TNF-α) production, we hypothesized that the mechanism of anesthetic immunoprotection is mediated through the vagus nerve. Methods. Male Sprague-Dawley rats underwent bilateral cervical vagotomy (n = 20) or sham operation (n = 6). Twenty-four hours postoperatively, vagotomized rats were randomized into 3 groups: LPS injection (V+LPS, n = 6), LPS injection followed by 60 minutes of isoflurane anesthesia (V+LPS+ISO, n = 7), or saline injection (V+S, n = 7). Sham animals were also given LPS (Sham+LPS). A sublethal dose of LPS (8 mg/kg) was used. Blood samples were collected via cardiac puncture 90 minutes after LPS or saline injection, and plasma was isolated for the measurement of cytokines by enzyme-linked immunosorbent assay. Statistical differences between groups were detected by 1-way analysis of variance. Results. Serum TNF-α was reduced significantly and interleukin (IL)-6 was abrogated completely among V+LPS+ISO rats, compared with both V+LPS and Sham+LPS animals (P ≤ .05 for all). In contrast, levels of the anti-inflammatory cytokine IL-10 were similar among all LPS groups. Conclusions. Isoflurane anesthesia administered simultaneously with the injection of LPS decreases serum production of TNF-α and IL-6 despite bilateral transection of the vagus nerve. Isoflurane-mediated attenuation of proinflammatory cytokine production occurs via a mechanism other than modulation of vagal output.
AB - Background. We have shown recently that volatile anesthetics significantly decrease inflammatory cytokine production and dramatically increase survival among rodents challenged with lipopolysaccharide (LPS). Because acetylcholine's interaction with nicotine receptors on tissue macrophages during vagus nerve stimulation has been implicated in the modulation of LPS-stimulated tumor necrosis factor alpha (TNF-α) production, we hypothesized that the mechanism of anesthetic immunoprotection is mediated through the vagus nerve. Methods. Male Sprague-Dawley rats underwent bilateral cervical vagotomy (n = 20) or sham operation (n = 6). Twenty-four hours postoperatively, vagotomized rats were randomized into 3 groups: LPS injection (V+LPS, n = 6), LPS injection followed by 60 minutes of isoflurane anesthesia (V+LPS+ISO, n = 7), or saline injection (V+S, n = 7). Sham animals were also given LPS (Sham+LPS). A sublethal dose of LPS (8 mg/kg) was used. Blood samples were collected via cardiac puncture 90 minutes after LPS or saline injection, and plasma was isolated for the measurement of cytokines by enzyme-linked immunosorbent assay. Statistical differences between groups were detected by 1-way analysis of variance. Results. Serum TNF-α was reduced significantly and interleukin (IL)-6 was abrogated completely among V+LPS+ISO rats, compared with both V+LPS and Sham+LPS animals (P ≤ .05 for all). In contrast, levels of the anti-inflammatory cytokine IL-10 were similar among all LPS groups. Conclusions. Isoflurane anesthesia administered simultaneously with the injection of LPS decreases serum production of TNF-α and IL-6 despite bilateral transection of the vagus nerve. Isoflurane-mediated attenuation of proinflammatory cytokine production occurs via a mechanism other than modulation of vagal output.
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U2 - 10.1016/j.surg.2005.06.057
DO - 10.1016/j.surg.2005.06.057
M3 - Article
C2 - 16269307
AN - SCOPUS:27544449492
SN - 0039-6060
VL - 138
SP - 766
EP - 771
JO - Surgery
JF - Surgery
IS - 4
ER -