AUTHOR=Berger Miles , Ponnusamy Vikram , Greene Nathaniel , Cooter Mary , Nadler Jacob W. , Friedman Allan , McDonagh David L. , Laskowitz Daniel T. , Newman Mark F. , Shaw Leslie M. , Warner David S. , Mathew Joseph P. , James Michael L. ,  For the MAD-PIA Investigators 

TITLE=The Effect of Propofol vs. Isoflurane Anesthesia on Postoperative Changes in Cerebrospinal Fluid Cytokine Levels: Results from a Randomized Trial

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01528

DOI=10.3389/fimmu.2017.01528

ISSN=1664-3224

ABSTRACT=<sec id="ST1"><title>Introduction</title><p>Aside from direct effects on neurotransmission, inhaled and intravenous anesthetics have immunomodulatory properties. <italic>In vitro</italic> 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.</p></sec><sec id="ST2"><title>Materials and methods</title><p>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 <uri xlink:href="http://www.clinicaltrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">http://www.clinicaltrials.gov</uri>, 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.</p></sec><sec id="ST3"><title>Results</title><p>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-1α, MIP-1β, and TNF-α. However, we found no difference in cytokine levels at baseline or 24 h after surgery between propofol- (<italic>n</italic> = 19) and isoflurane-treated (<italic>n</italic> = 21) patients (<italic>p</italic> &gt; 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.</p></sec><sec id="ST4"><title>Discussion</title><p>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.</p></sec>