Effects of anesthesia on lipopolysaccharide-induced changes in serum cytokines

Sasha D. Adams, Ravi Radhakrishnan, Kenneth S. Helmer, David W. Mercer

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: The pathophysiology of sepsis is incompletely understood, however alterations in systemic inflammation and serum cytokines are thought to play a central role. In the rat, ketamine, but not isoflurane, prevents hepatic injury from lipopolysaccharide (LPS). The effect of these anesthetics on the systemic inflammatory response and other organs remains to be fully elucidated. We hypothesized that ketamine, but not isoflurane, would blunt the cytokine response to LPS administration. Methods: Male rats received no anesthesia, intraperitoneal ketamine (70 mg/kg), or inhalational isoflurane. One hour later, LPS (20 mg/kg, intraperitoneal) or saline was given for 5 hours and rats were killed. Gastric fluid volumes were determined as an index of gastric emptying. Serum was collected and cytokines measured via a multiplexed suspension immunoassay. Results: In nonanesthetized rats, LPS increased gastric luminal fluid accumulation and serum levels of proinflammatory cytokines when compared with saline controls. Anesthesia with either ketamine or isoflurane caused a significant reduction in LPS-induced changes in serum cytokines, although ketamine had a more dramatic reduction in tumor necrosis factor alpha levels than did isoflurane. Both anesthetics reduced the interleukin IL-6/IL-10 ratio in response to LPS when compared with LPS alone. Ketamine, but not isoflurane, prevented LPS-induced gastric luminal fluid accumulation. Conclusions: These data indicate that both ketamine and isoflurane diminish the systemic inflammatory response to LPS in the rat as measured by serum cytokines and a reduced IL-6/IL-10 ratio. However, only ketamine improves LPS-induced gastric dysfunction, perhaps secondary to its ability to reduce serum tumor necrosis factor alpha levels more effectively.

Original languageEnglish (US)
Pages (from-to)170-174
Number of pages5
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume65
Issue number1
DOIs
StatePublished - Jul 2008
Externally publishedYes

Fingerprint

Lipopolysaccharides
Ketamine
Isoflurane
Anesthesia
Cytokines
Serum
Stomach
Interleukin-6
Interleukin-10
Anesthetics
Tumor Necrosis Factor-alpha
Gastric Emptying
Immunoassay
Sepsis
Suspensions
Inflammation
Liver
Wounds and Injuries

Keywords

  • Inflammation
  • Isoflurane
  • Ketamine
  • Sepsis

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

Effects of anesthesia on lipopolysaccharide-induced changes in serum cytokines. / Adams, Sasha D.; Radhakrishnan, Ravi; Helmer, Kenneth S.; Mercer, David W.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 65, No. 1, 07.2008, p. 170-174.

Research output: Contribution to journalArticle

@article{48c894ba4802493d99ff3635678b706b,
title = "Effects of anesthesia on lipopolysaccharide-induced changes in serum cytokines",
abstract = "Background: The pathophysiology of sepsis is incompletely understood, however alterations in systemic inflammation and serum cytokines are thought to play a central role. In the rat, ketamine, but not isoflurane, prevents hepatic injury from lipopolysaccharide (LPS). The effect of these anesthetics on the systemic inflammatory response and other organs remains to be fully elucidated. We hypothesized that ketamine, but not isoflurane, would blunt the cytokine response to LPS administration. Methods: Male rats received no anesthesia, intraperitoneal ketamine (70 mg/kg), or inhalational isoflurane. One hour later, LPS (20 mg/kg, intraperitoneal) or saline was given for 5 hours and rats were killed. Gastric fluid volumes were determined as an index of gastric emptying. Serum was collected and cytokines measured via a multiplexed suspension immunoassay. Results: In nonanesthetized rats, LPS increased gastric luminal fluid accumulation and serum levels of proinflammatory cytokines when compared with saline controls. Anesthesia with either ketamine or isoflurane caused a significant reduction in LPS-induced changes in serum cytokines, although ketamine had a more dramatic reduction in tumor necrosis factor alpha levels than did isoflurane. Both anesthetics reduced the interleukin IL-6/IL-10 ratio in response to LPS when compared with LPS alone. Ketamine, but not isoflurane, prevented LPS-induced gastric luminal fluid accumulation. Conclusions: These data indicate that both ketamine and isoflurane diminish the systemic inflammatory response to LPS in the rat as measured by serum cytokines and a reduced IL-6/IL-10 ratio. However, only ketamine improves LPS-induced gastric dysfunction, perhaps secondary to its ability to reduce serum tumor necrosis factor alpha levels more effectively.",
keywords = "Inflammation, Isoflurane, Ketamine, Sepsis",
author = "Adams, {Sasha D.} and Ravi Radhakrishnan and Helmer, {Kenneth S.} and Mercer, {David W.}",
year = "2008",
month = "7",
doi = "10.1097/TA.0b013e31805824ca",
language = "English (US)",
volume = "65",
pages = "170--174",
journal = "Journal of Trauma and Acute Care Surgery",
issn = "2163-0755",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Effects of anesthesia on lipopolysaccharide-induced changes in serum cytokines

AU - Adams, Sasha D.

AU - Radhakrishnan, Ravi

AU - Helmer, Kenneth S.

AU - Mercer, David W.

PY - 2008/7

Y1 - 2008/7

N2 - Background: The pathophysiology of sepsis is incompletely understood, however alterations in systemic inflammation and serum cytokines are thought to play a central role. In the rat, ketamine, but not isoflurane, prevents hepatic injury from lipopolysaccharide (LPS). The effect of these anesthetics on the systemic inflammatory response and other organs remains to be fully elucidated. We hypothesized that ketamine, but not isoflurane, would blunt the cytokine response to LPS administration. Methods: Male rats received no anesthesia, intraperitoneal ketamine (70 mg/kg), or inhalational isoflurane. One hour later, LPS (20 mg/kg, intraperitoneal) or saline was given for 5 hours and rats were killed. Gastric fluid volumes were determined as an index of gastric emptying. Serum was collected and cytokines measured via a multiplexed suspension immunoassay. Results: In nonanesthetized rats, LPS increased gastric luminal fluid accumulation and serum levels of proinflammatory cytokines when compared with saline controls. Anesthesia with either ketamine or isoflurane caused a significant reduction in LPS-induced changes in serum cytokines, although ketamine had a more dramatic reduction in tumor necrosis factor alpha levels than did isoflurane. Both anesthetics reduced the interleukin IL-6/IL-10 ratio in response to LPS when compared with LPS alone. Ketamine, but not isoflurane, prevented LPS-induced gastric luminal fluid accumulation. Conclusions: These data indicate that both ketamine and isoflurane diminish the systemic inflammatory response to LPS in the rat as measured by serum cytokines and a reduced IL-6/IL-10 ratio. However, only ketamine improves LPS-induced gastric dysfunction, perhaps secondary to its ability to reduce serum tumor necrosis factor alpha levels more effectively.

AB - Background: The pathophysiology of sepsis is incompletely understood, however alterations in systemic inflammation and serum cytokines are thought to play a central role. In the rat, ketamine, but not isoflurane, prevents hepatic injury from lipopolysaccharide (LPS). The effect of these anesthetics on the systemic inflammatory response and other organs remains to be fully elucidated. We hypothesized that ketamine, but not isoflurane, would blunt the cytokine response to LPS administration. Methods: Male rats received no anesthesia, intraperitoneal ketamine (70 mg/kg), or inhalational isoflurane. One hour later, LPS (20 mg/kg, intraperitoneal) or saline was given for 5 hours and rats were killed. Gastric fluid volumes were determined as an index of gastric emptying. Serum was collected and cytokines measured via a multiplexed suspension immunoassay. Results: In nonanesthetized rats, LPS increased gastric luminal fluid accumulation and serum levels of proinflammatory cytokines when compared with saline controls. Anesthesia with either ketamine or isoflurane caused a significant reduction in LPS-induced changes in serum cytokines, although ketamine had a more dramatic reduction in tumor necrosis factor alpha levels than did isoflurane. Both anesthetics reduced the interleukin IL-6/IL-10 ratio in response to LPS when compared with LPS alone. Ketamine, but not isoflurane, prevented LPS-induced gastric luminal fluid accumulation. Conclusions: These data indicate that both ketamine and isoflurane diminish the systemic inflammatory response to LPS in the rat as measured by serum cytokines and a reduced IL-6/IL-10 ratio. However, only ketamine improves LPS-induced gastric dysfunction, perhaps secondary to its ability to reduce serum tumor necrosis factor alpha levels more effectively.

KW - Inflammation

KW - Isoflurane

KW - Ketamine

KW - Sepsis

UR - http://www.scopus.com/inward/record.url?scp=67649999239&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649999239&partnerID=8YFLogxK

U2 - 10.1097/TA.0b013e31805824ca

DO - 10.1097/TA.0b013e31805824ca

M3 - Article

VL - 65

SP - 170

EP - 174

JO - Journal of Trauma and Acute Care Surgery

JF - Journal of Trauma and Acute Care Surgery

SN - 2163-0755

IS - 1

ER -