The effect of Propofol vs. isoflurane anesthesia on postoperative changes in cerebrospinal fluid cytokine levels: Results from a randomized trial

doi:10.3389/fimmu.2017.01528

The effect of Propofol vs. isoflurane anesthesia on postoperative changes in cerebrospinal fluid cytokine levels: Results from a randomized trial

Anesthesiology

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27 Scopus citations

Abstract

Introduction: Aside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. In vitro and mouse model studies suggest that propofol inhibits, while isoflurane increases, neuroinflammation. If these findings translate to humans, they could be clinically important since neuroinflammation has detrimental effects on neurocognitive function in numerous disease states. Materials and methods: To examine whether propofol and isoflurane differentially modulate neuroinflammation in humans,cytokines were measured in a secondary analysis of cerebrospinal fluid (CSF) samples from patients prospectively randomized to receive anesthetic maintenance with propofol vs. isoflurane (registered with http://www.clinicaltrials.gov, identifier NCT01640275). We measured CSF levels of EGF, eotaxin, G-CSF, GM-CSF, IFN-α2, IL-1RA, IL-6, IL-7, IL-8, IL-10, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α before and 24 h after intracranial surgery in these study patients. Results: After Bonferroni correction for multiple comparisons, we found significant increases from before to 24 h after surgery in G-CSF, IL-10, IL-1RA, IL-6, IL-8, IP-10, MCP-1, MIP-1a, MIP-1β, and TNF-α. However, we found no difference in cytokine levels at baseline or 24 h after surgery between propofol- (n = 19) and isoflurane-treated (n = 21) patients (p > 0.05 for all comparisons). Increases in CSF IL-6, IL-8, IP-10, and MCP-1 levels directly correlated with each other and with postoperative CSF elevations in tau, a neural injury biomarker. We observed CSF cytokine increases up to 10-fold higher after intracranial surgery than previously reported after other types of surgery. Discussion: These data clarify the magnitude of neuroinflammation after intracranial surgery, and raise the possibility that a coordinated neuroinflammatory response may play a role in neural injury after surgery.

Original language	English
Article number	1528
Journal	Frontiers in Immunology
Volume	8
Issue number	NOV
DOIs	https://doi.org/10.3389/fimmu.2017.01528
State	Published - Nov 13 2017

Bibliographical note

Funding Information:
This paper is dedicated to the memory of Dr. William L. Young. This project was supported by Duke Anesthesiology departmental funds. MB also acknowledges support from a DREAM Innovation Grant from Duke Anesthesiology, an IARS Mentored Research Award, NIH T32 grant #GM08600 (to DW), NIH R03 AG050918, NIH K76 AG057022, a Jahnigen Scholars Fellowship award, a small project grant from the American Geriatrics Society, and additional support from NIA P30-AG028716. VP was supported by a Foundation for Anesthesia Education and Research (FAER) FAER Research Fellowship.

Publisher Copyright:
© 2017 Berger, Ponnusamy, Greene, Cooter, Nadler, Friedman, McDonagh, Laskowitz, Newman, Shaw, Warner, Mathew and James.

Keywords

Anesthesia
Cerebrospinal fluid
Cytokine
Inflammation
Isoflurane
Neuroinflammation
Propofol
Surgery

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.3389/fimmu.2017.01528

Cite this

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title = "The effect of Propofol vs. isoflurane anesthesia on postoperative changes in cerebrospinal fluid cytokine levels: Results from a randomized trial",

abstract = "Introduction: Aside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. In vitro and mouse model studies suggest that propofol inhibits, while isoflurane increases, neuroinflammation. If these findings translate to humans, they could be clinically important since neuroinflammation has detrimental effects on neurocognitive function in numerous disease states. Materials and methods: To examine whether propofol and isoflurane differentially modulate neuroinflammation in humans,cytokines were measured in a secondary analysis of cerebrospinal fluid (CSF) samples from patients prospectively randomized to receive anesthetic maintenance with propofol vs. isoflurane (registered with http://www.clinicaltrials.gov, identifier NCT01640275). We measured CSF levels of EGF, eotaxin, G-CSF, GM-CSF, IFN-α2, IL-1RA, IL-6, IL-7, IL-8, IL-10, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α before and 24 h after intracranial surgery in these study patients. Results: After Bonferroni correction for multiple comparisons, we found significant increases from before to 24 h after surgery in G-CSF, IL-10, IL-1RA, IL-6, IL-8, IP-10, MCP-1, MIP-1a, MIP-1β, and TNF-α. However, we found no difference in cytokine levels at baseline or 24 h after surgery between propofol- (n = 19) and isoflurane-treated (n = 21) patients (p > 0.05 for all comparisons). Increases in CSF IL-6, IL-8, IP-10, and MCP-1 levels directly correlated with each other and with postoperative CSF elevations in tau, a neural injury biomarker. We observed CSF cytokine increases up to 10-fold higher after intracranial surgery than previously reported after other types of surgery. Discussion: These data clarify the magnitude of neuroinflammation after intracranial surgery, and raise the possibility that a coordinated neuroinflammatory response may play a role in neural injury after surgery.",

keywords = "Anesthesia, Cerebrospinal fluid, Cytokine, Inflammation, Isoflurane, Neuroinflammation, Propofol, Surgery",

author = "Miles Berger and Vikram Ponnusamy and Nathaniel Greene and Mary Cooter and Nadler, {Jacob W.} and Allan Friedman and McDonagh, {David L.} and Laskowitz, {Daniel T.} and Newman, {Mark F.} and Shaw, {Leslie M.} and Warner, {David S.} and Mathew, {Joseph P.} and James, {Michael L.} and Carter, {James H.} and Shivanandan Lad and Ali Zomorodi and John Sampson and Takanori Fukushima and Owoicho Adogwa and Karen Clemmons and Carlos Conde and Omowunmi Olaleye and Naraida Balajonda and Jhoanna Aquino and Bonita Funk and Li, {Yi Ju} and White, {William D.}",

note = "Funding Information: This paper is dedicated to the memory of Dr. William L. Young. This project was supported by Duke Anesthesiology departmental funds. MB also acknowledges support from a DREAM Innovation Grant from Duke Anesthesiology, an IARS Mentored Research Award, NIH T32 grant #GM08600 (to DW), NIH R03 AG050918, NIH K76 AG057022, a Jahnigen Scholars Fellowship award, a small project grant from the American Geriatrics Society, and additional support from NIA P30-AG028716. VP was supported by a Foundation for Anesthesia Education and Research (FAER) FAER Research Fellowship. Publisher Copyright: {\textcopyright} 2017 Berger, Ponnusamy, Greene, Cooter, Nadler, Friedman, McDonagh, Laskowitz, Newman, Shaw, Warner, Mathew and James.",

year = "2017",

month = nov,

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doi = "10.3389/fimmu.2017.01528",

language = "English",

volume = "8",

number = "NOV",

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TY - JOUR

T1 - The effect of Propofol vs. isoflurane anesthesia on postoperative changes in cerebrospinal fluid cytokine levels

T2 - Results from a randomized trial

AU - Berger, Miles

AU - Ponnusamy, Vikram

AU - Greene, Nathaniel

AU - Cooter, Mary

AU - Nadler, Jacob W.

AU - Friedman, Allan

AU - McDonagh, David L.

AU - Laskowitz, Daniel T.

AU - Newman, Mark F.

AU - Shaw, Leslie M.

AU - Warner, David S.

AU - Mathew, Joseph P.

AU - James, Michael L.

AU - Carter, James H.

AU - Lad, Shivanandan

AU - Zomorodi, Ali

AU - Sampson, John

AU - Fukushima, Takanori

AU - Adogwa, Owoicho

AU - Clemmons, Karen

AU - Conde, Carlos

AU - Olaleye, Omowunmi

AU - Balajonda, Naraida

AU - Aquino, Jhoanna

AU - Funk, Bonita

AU - Li, Yi Ju

AU - White, William D.

N1 - Funding Information: This paper is dedicated to the memory of Dr. William L. Young. This project was supported by Duke Anesthesiology departmental funds. MB also acknowledges support from a DREAM Innovation Grant from Duke Anesthesiology, an IARS Mentored Research Award, NIH T32 grant #GM08600 (to DW), NIH R03 AG050918, NIH K76 AG057022, a Jahnigen Scholars Fellowship award, a small project grant from the American Geriatrics Society, and additional support from NIA P30-AG028716. VP was supported by a Foundation for Anesthesia Education and Research (FAER) FAER Research Fellowship. Publisher Copyright: © 2017 Berger, Ponnusamy, Greene, Cooter, Nadler, Friedman, McDonagh, Laskowitz, Newman, Shaw, Warner, Mathew and James.

PY - 2017/11/13

Y1 - 2017/11/13

N2 - Introduction: Aside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. In vitro and mouse model studies suggest that propofol inhibits, while isoflurane increases, neuroinflammation. If these findings translate to humans, they could be clinically important since neuroinflammation has detrimental effects on neurocognitive function in numerous disease states. Materials and methods: To examine whether propofol and isoflurane differentially modulate neuroinflammation in humans,cytokines were measured in a secondary analysis of cerebrospinal fluid (CSF) samples from patients prospectively randomized to receive anesthetic maintenance with propofol vs. isoflurane (registered with http://www.clinicaltrials.gov, identifier NCT01640275). We measured CSF levels of EGF, eotaxin, G-CSF, GM-CSF, IFN-α2, IL-1RA, IL-6, IL-7, IL-8, IL-10, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α before and 24 h after intracranial surgery in these study patients. Results: After Bonferroni correction for multiple comparisons, we found significant increases from before to 24 h after surgery in G-CSF, IL-10, IL-1RA, IL-6, IL-8, IP-10, MCP-1, MIP-1a, MIP-1β, and TNF-α. However, we found no difference in cytokine levels at baseline or 24 h after surgery between propofol- (n = 19) and isoflurane-treated (n = 21) patients (p > 0.05 for all comparisons). Increases in CSF IL-6, IL-8, IP-10, and MCP-1 levels directly correlated with each other and with postoperative CSF elevations in tau, a neural injury biomarker. We observed CSF cytokine increases up to 10-fold higher after intracranial surgery than previously reported after other types of surgery. Discussion: These data clarify the magnitude of neuroinflammation after intracranial surgery, and raise the possibility that a coordinated neuroinflammatory response may play a role in neural injury after surgery.

AB - Introduction: Aside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. In vitro and mouse model studies suggest that propofol inhibits, while isoflurane increases, neuroinflammation. If these findings translate to humans, they could be clinically important since neuroinflammation has detrimental effects on neurocognitive function in numerous disease states. Materials and methods: To examine whether propofol and isoflurane differentially modulate neuroinflammation in humans,cytokines were measured in a secondary analysis of cerebrospinal fluid (CSF) samples from patients prospectively randomized to receive anesthetic maintenance with propofol vs. isoflurane (registered with http://www.clinicaltrials.gov, identifier NCT01640275). We measured CSF levels of EGF, eotaxin, G-CSF, GM-CSF, IFN-α2, IL-1RA, IL-6, IL-7, IL-8, IL-10, IP-10, MCP-1, MIP-1α, MIP-1β, and TNF-α before and 24 h after intracranial surgery in these study patients. Results: After Bonferroni correction for multiple comparisons, we found significant increases from before to 24 h after surgery in G-CSF, IL-10, IL-1RA, IL-6, IL-8, IP-10, MCP-1, MIP-1a, MIP-1β, and TNF-α. However, we found no difference in cytokine levels at baseline or 24 h after surgery between propofol- (n = 19) and isoflurane-treated (n = 21) patients (p > 0.05 for all comparisons). Increases in CSF IL-6, IL-8, IP-10, and MCP-1 levels directly correlated with each other and with postoperative CSF elevations in tau, a neural injury biomarker. We observed CSF cytokine increases up to 10-fold higher after intracranial surgery than previously reported after other types of surgery. Discussion: These data clarify the magnitude of neuroinflammation after intracranial surgery, and raise the possibility that a coordinated neuroinflammatory response may play a role in neural injury after surgery.

KW - Anesthesia

KW - Cerebrospinal fluid

KW - Cytokine

KW - Inflammation

KW - Isoflurane

KW - Neuroinflammation

KW - Propofol

KW - Surgery

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The effect of Propofol vs. isoflurane anesthesia on postoperative changes in cerebrospinal fluid cytokine levels: Results from a randomized trial

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

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