Effects of an intravenous ketamine infusion on inflammatory cytokine levels in male and female Sprague-Dawley rats.
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
04 Apr 2022
04 Apr 2022
Historique:
received:
27
11
2021
accepted:
20
03
2022
entrez:
5
4
2022
pubmed:
6
4
2022
medline:
7
4
2022
Statut:
epublish
Résumé
Ketamine, a multimodal dissociative anesthetic drug, is widely used as an analgesic following traumatic injury. Although ketamine may produce anti-inflammatory effects when administered after injury, the immunomodulatory properties of intravenous (IV) ketamine in a non-inflammatory condition are unclear. In addition, most preclinical studies use an intraperitoneal (IP) injection of ketamine, which limits its clinical translation as patients usually receive an IV ketamine infusion after injury. Here, we administered sub-anesthetic doses of a single IV ketamine infusion (0, 10, or 40 mg/kg) to male and female Sprague-Dawley rats over a 2-h period. We collected blood samples at 2- and 4-h post-ketamine infusion to determine plasma inflammatory cytokine levels using multiplex immunoassays. The 10 mg/kg ketamine infusion reduced spontaneous locomotor activity in male and female rats, while the 40 mg/kg infusion stimulated activity in female, but not male, rats. The IV ketamine infusion produced dose-dependent and sex-specific effects on plasma inflammatory cytokine levels. A ketamine infusion reduced KC/GRO and tumor necrosis factor alpha (TNF-α) levels in both male and female rats, interleukin-6 (IL-6) levels in female rats, and interleukin-10 (IL-10) levels in male rats. However, most cytokine levels returned to control levels at 4-h post-infusion, except for IL-6 levels in male rats and TNF-α levels in female rats, indicating a different trajectory of certain cytokine changes over time following ketamine administration. The current findings suggest that sub-anesthetic doses of an IV ketamine infusion may produce sex-related differences in the effects on peripheral inflammatory markers in rodents, and further research is warranted to determine potential therapeutic effects of an IV ketamine infusion in an inflammatory condition.
Sections du résumé
BACKGROUND
BACKGROUND
Ketamine, a multimodal dissociative anesthetic drug, is widely used as an analgesic following traumatic injury. Although ketamine may produce anti-inflammatory effects when administered after injury, the immunomodulatory properties of intravenous (IV) ketamine in a non-inflammatory condition are unclear. In addition, most preclinical studies use an intraperitoneal (IP) injection of ketamine, which limits its clinical translation as patients usually receive an IV ketamine infusion after injury.
METHODS
METHODS
Here, we administered sub-anesthetic doses of a single IV ketamine infusion (0, 10, or 40 mg/kg) to male and female Sprague-Dawley rats over a 2-h period. We collected blood samples at 2- and 4-h post-ketamine infusion to determine plasma inflammatory cytokine levels using multiplex immunoassays.
RESULTS
RESULTS
The 10 mg/kg ketamine infusion reduced spontaneous locomotor activity in male and female rats, while the 40 mg/kg infusion stimulated activity in female, but not male, rats. The IV ketamine infusion produced dose-dependent and sex-specific effects on plasma inflammatory cytokine levels. A ketamine infusion reduced KC/GRO and tumor necrosis factor alpha (TNF-α) levels in both male and female rats, interleukin-6 (IL-6) levels in female rats, and interleukin-10 (IL-10) levels in male rats. However, most cytokine levels returned to control levels at 4-h post-infusion, except for IL-6 levels in male rats and TNF-α levels in female rats, indicating a different trajectory of certain cytokine changes over time following ketamine administration.
CONCLUSIONS
CONCLUSIONS
The current findings suggest that sub-anesthetic doses of an IV ketamine infusion may produce sex-related differences in the effects on peripheral inflammatory markers in rodents, and further research is warranted to determine potential therapeutic effects of an IV ketamine infusion in an inflammatory condition.
Identifiants
pubmed: 35379262
doi: 10.1186/s12974-022-02434-w
pii: 10.1186/s12974-022-02434-w
pmc: PMC8981848
doi:
Substances chimiques
Analgesics
0
Cytokines
0
Ketamine
690G0D6V8H
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
75Subventions
Organisme : TriService Nursing Research Program
ID : N21-07
Organisme : TriService Nursing Research Program
ID : N21-07
Organisme : TriService Nursing Research Program
ID : N21-07
Organisme : TriService Nursing Research Program
ID : N21-07
Organisme : TriService Nursing Research Program
ID : N21-07
Organisme : TriService Nursing Research Program
ID : N21-07
Organisme : TriService Nursing Research Program
ID : N21-07
Informations de copyright
© 2022. The Author(s).
Références
Innate Immun. 2008 Apr;14(2):117-24
pubmed: 18713728
Transl Neurosci. 2021 May 26;12(1):218-236
pubmed: 34079622
Toxicol Appl Pharmacol. 2008 Apr 1;228(1):105-13
pubmed: 18191973
Behav Brain Res. 2020 Feb 3;379:112302
pubmed: 31655095
Exp Ther Med. 2013 Apr;5(4):1093-1096
pubmed: 23596475
Neuroscience. 2017 Feb 20;343:30-38
pubmed: 27916727
J Trauma. 2011 Jun;70(6):1471-9
pubmed: 21817985
Nat Commun. 2020 Jul 10;11(1):3459
pubmed: 32651360
J Surg Res. 2015 Apr;194(2):599-613
pubmed: 25614361
CNS Neurosci Ther. 2013 Jun;19(6):403-10
pubmed: 23574634
Front Pharmacol. 2017 Mar 20;8:139
pubmed: 28373844
J Trauma Acute Care Surg. 2015 Apr;78(4):784-92
pubmed: 25807407
Tohoku J Exp Med. 2003 Jun;200(2):85-92
pubmed: 12962405
Behav Brain Res. 2020 Jan 27;378:112259
pubmed: 31560919
Biochim Biophys Acta. 2011 May;1813(5):878-88
pubmed: 21296109
Acta Anaesthesiol Scand. 1999 Nov;43(10):1011-6
pubmed: 10593463
J Spec Oper Med. 2014 Spring;14(1):13-25
pubmed: 24604434
Curr Psychiatry Rep. 2015 Oct;17(10):78
pubmed: 26272539
Toxicol Appl Pharmacol. 2005 Apr 1;204(1):27-35
pubmed: 15781291
Anesth Analg. 1990 Jun;70(6):608-17
pubmed: 2188526
Behav Brain Res. 2020 Feb 3;379:112267
pubmed: 31593789
Arch Med Sci. 2015 Dec 10;11(6):1296-302
pubmed: 26788093
Psychiatry Res. 2018 Nov;269:207-211
pubmed: 30153598
Acta Anaesthesiol Belg. 2011;62(1):47-58
pubmed: 21612145
EBioMedicine. 2019 Dec;50:290-305
pubmed: 31753725
Brain Behav Immun. 2010 Jan;24(1):54-7
pubmed: 19520155
CNS Neurosci Ther. 2013 Jun;19(6):390-5
pubmed: 23480625
Am J Physiol Regul Integr Comp Physiol. 2007 Jul;293(1):R145-51
pubmed: 17428894
Endocrinology. 2007 Aug;148(8):3758-64
pubmed: 17510233
Am J Vet Res. 2008 Feb;69(2):228-32
pubmed: 18241020
Fundam Clin Pharmacol. 2020 Apr;34(2):229-237
pubmed: 31514224
Front Neuroendocrinol. 2018 Jul;50:52-66
pubmed: 29753798
Mil Med. 2020 Jan 7;185(Suppl 1):136-142
pubmed: 32074369
Nat Rev Immunol. 2016 Oct;16(10):626-38
pubmed: 27546235
Anesth Analg. 1998 Aug;87(2):266-71
pubmed: 9706914
Pharmacol Rep. 2021 Apr;73(2):525-535
pubmed: 33393059
AANA J. 2018 Oct;86(5):393-400
pubmed: 31584409
J Neuroinflammation. 2021 Sep 15;18(1):200
pubmed: 34526064
Anesth Analg. 2012 Oct;115(4):934-43
pubmed: 22826531
Biochem Biophys Res Commun. 1993 Nov 30;197(1):319-25
pubmed: 8250941
Neuroscience. 2017 Jun 14;353:17-25
pubmed: 28433652
Neurocrit Care. 2014 Aug;21(1):163-73
pubmed: 24515638
Atherosclerosis. 2006 Jan;184(1):216-24
pubmed: 15993885
Curr Anesthesiol Rep. 2018;8(3):279-289
pubmed: 30147453
Br J Anaesth. 2007 Oct;99(4):522-7
pubmed: 17681970
Int Immunopharmacol. 2014 Nov;23(1):14-26
pubmed: 25133650
Nat Immunol. 2001 Sep;2(9):777-80
pubmed: 11526384
Psychopharmacology (Berl). 2017 Sep;234(18):2683-2696
pubmed: 28589265
J Exp Med. 1991 Nov 1;174(5):1209-20
pubmed: 1940799
Acta Anaesthesiol Scand. 1992 Jul;36(5):483-5
pubmed: 1632173
J Pharmacol Exp Ther. 2018 Dec;367(3):393-404
pubmed: 30213876
Anesth Analg. 2002 Sep;95(3):531-6, table of contents
pubmed: 12198030
Transl Psychiatry. 2020 Jul 22;10(1):246
pubmed: 32699226
Crit Care Med. 1995 Dec;23(12):2008-14
pubmed: 7497723
Neuropharmacology. 2013 Jul;70:27-34
pubmed: 23337256
Clin Invest Med. 2014 Jun 01;37(3):E124
pubmed: 24895987
Front Neuroendocrinol. 2018 Jul;50:91-106
pubmed: 29935190
Pharmacol Biochem Behav. 2017 Feb;153:130-140
pubmed: 28024909
Ann Clin Lab Sci. 2004 Spring;34(2):181-6
pubmed: 15228231
Arch Immunol Ther Exp (Warsz). 2019 Jun;67(3):143-151
pubmed: 31032529
Drug Des Devel Ther. 2018 Apr 16;12:845-853
pubmed: 29713142
Anesthesiology. 2001 Oct;95(4):928-32
pubmed: 11605934
Behav Brain Res. 2015 Oct 15;293:198-202
pubmed: 26209292
Prehosp Emerg Care. 2017 Nov-Dec;21(6):744-749
pubmed: 28829661
Mil Med. 2015 Mar;180(3 Suppl):14-8
pubmed: 25747624
Crit Care Med. 1998 Sep;26(9):1545-9
pubmed: 9751591
Mol Med Rep. 2013 Jul;8(1):217-20
pubmed: 23660699
Pharmacol Biochem Behav. 2020 Dec;199:173042
pubmed: 32976859
Biol Psychiatry. 2015 Feb 1;77(3):e19-e20
pubmed: 25104172
Mediators Inflamm. 2009;2009:705379
pubmed: 19343193
Biol Psychol. 2006 Mar;71(3):236-9
pubmed: 16098655
Anesth Analg. 2017 Apr;124(4):1237-1243
pubmed: 28079589
Transl Psychiatry. 2018 Nov 30;8(1):263
pubmed: 30504810
Anesth Analg. 1999 Sep;89(3):665-9
pubmed: 10475301
Neurosci Lett. 2018 Jan 18;664:160-166
pubmed: 29133177
Curr Opin Behav Sci. 2018 Oct;23:36-41
pubmed: 30038955