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

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27 Scopus citations


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, 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 languageEnglish
Article number1528
JournalFrontiers in Immunology
Issue numberNOV
StatePublished - 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.


  • Anesthesia
  • Cerebrospinal fluid
  • Cytokine
  • Inflammation
  • Isoflurane
  • Neuroinflammation
  • Propofol
  • Surgery

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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