title: 3,4-methylenedioxymethamphetamine (MDMA--Ecstasy) decreases neutrophil activity through the glucocorticoid pathway and impairs host resistance to Listeria monocytogenes infection in mice.
abstract: Ecstasy is the popular name of the abuse drug 3,4-methylenedioxymethamphetamine (MDMA) that decreases immunity in animals. The mechanisms that generate such alterations are still controversial. Seven independent pharmacological approaches were performed in mice to identify the possible mechanisms underlying the decrease of neutrophil activity induced by MDMA and the possible effects of MDMA on host resistance to Listeria monocytogenes. Our data showed that MDMA (10 mg kg(-1)) administration decreases NFκB expression in circulating neutrophils. Metyrapone or RU-486 administration prior to MDMA treatment abrogated MDMA effects on neutrophil activity and NFκB expression, while 6-OHDA or ICI-118,551 administration did not. As MDMA treatment increased the plasmatic levels of adrenaline and noradrenaline, propranolol pre-treatment effects were also evaluated. Propranolol suppressed both MDMA-induced increase in corticosterone serum levels and its effects on neutrophil activity. In a L. monocytogenes experimental infection context, we showed that MDMA: induced myelosuppression by decreasing granulocyte-macrophage hematopoietic progenitors (CFU-GM) in the bone marrow but increased CFU-GM in the spleen; decreased circulating leukocytes and bone marrow cellularity and increased spleen cellularity; decreased pro-inflammatory cytokine (IL-12p70, TNF, IFN-γ, IL-6) and chemokine (MCP-1) production 24 h after the infection; increased the production of pro-inflammatory cytokines and chemokines 72 h after infection and decreased IL-10 levels at all time points analyzed. It was proposed that MDMA immunosuppressive effects on neutrophil activity and host resistance to L monocytogenes rely on NFκB signaling, being mediated by HPA axis activity and corticosterone.
authors.affiliation: Neuroimmunomodulation Research Group, Department of Pathology, School of Veterinary Medicine, University of São Paulo, Av. Prof. Dr. Orlando Marques de Paiva, 87 - CEP, 05508-270, São Paulo, SP, Brazil.
authors.forename: V
authors.initials: V
authors.lastname: Ferraz-de-Paula
authors.forename: A
authors.initials: A
authors.lastname: Ribeiro
authors.forename: J
authors.initials: J
authors.lastname: Souza-Queiroz
authors.forename: M L
authors.initials: ML
authors.lastname: Pinheiro
authors.forename: J F
authors.initials: JF
authors.lastname: Vecina
authors.forename: D P M
authors.initials: DP
authors.lastname: Souza
authors.forename: W M
authors.initials: WM
authors.lastname: Quinteiro-Filho
authors.forename: R L M
authors.initials: RL
authors.lastname: Moreau
authors.forename: M L S
authors.initials: ML
authors.lastname: Queiroz
authors.forename: J
authors.initials: J
authors.lastname: Palermo-Neto
mesh_terms: D000818:Animals; D005938:Glucocorticoids / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008089:Listeria monocytogenes / Q000187:drug effects* / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D005938:Glucocorticoids; D018817:N-Methyl-3,4-methylenedioxyamphetamine
references.citation: Brain Behav Immun. 2008 Oct;22(7):1056-1065
references.pmid: 18420376
references.citation: Life Sci. 2000 Aug 18;67(13):1601-12
references.pmid: 10983854
references.citation: J Neuroimmunol. 2001 Mar 1;114(1-2):19-27
references.pmid: 11240011
references.citation: J Infect Dis. 2009 Oct 15;200(8):1247-50
references.pmid: 19758099
references.citation: J Pharmacol Exp Ther. 2004 Apr;309(1):285-92
references.pmid: 14722327
references.citation: Ann N Y Acad Sci. 2002 Jun;965:421-33
references.pmid: 12105117
references.citation: Immunol Lett. 2001 Sep 3;78(2):67-73
references.pmid: 11672589
references.citation: Immunopharmacol Immunotoxicol. 2010 Jun;32(2):265-71
references.pmid: 20105082
references.citation: Nat Rev Endocrinol. 2013 Nov;9(11):670-86
references.pmid: 24080732
references.citation: Immunopharmacology. 1998 Jan;38(3):253-60
references.pmid: 9506825
references.citation: Inflamm Allergy Drug Targets. 2012 Jun;11(3):170-80
references.pmid: 22280241
references.citation: Vet Immunol Immunopathol. 2003 Sep 15;95(1-2):11-9
references.pmid: 12969632
references.citation: Clin Infect Dis. 2005 Nov 15;41 Suppl 7:S459-64
references.pmid: 16237648
references.citation: BMC Mol Biol. 2007 Jul 31;8:64
references.pmid: 17663801
references.citation: Hum Psychopharmacol. 2013 Jul;28(4):289-307
references.pmid: 23881877
references.citation: Eur J Pharmacol. 2007 Oct 31;572(2-3):228-38
references.pmid: 17689526
references.citation: Brain Behav Immun. 2008 Aug;22(6):912-22
references.pmid: 18280699
references.citation: Br J Pharmacol. 2010 Sep;161(1):17-32
references.pmid: 20718737
references.citation: J Immunol Methods. 1989 Feb 8;117(1):53-8
references.pmid: 2913161
references.citation: J Pharmacol Exp Ther. 2012 Feb;340(2):286-94
references.pmid: 22034656
references.citation: J Immunol. 1995 Nov 15;155(10):4613-20
references.pmid: 7594460
references.citation: J Neuroimmunol. 1999 Nov 15;101(2):201-4
references.pmid: 10580803
references.citation: Trends Pharmacol Sci. 2004 Oct;25(10):505-8
references.pmid: 15380932
references.citation: J Pharmacol Exp Ther. 2005 Jan;312(1):134-43
references.pmid: 15331655
references.citation: Trends Immunol. 2012 Oct;33(10):488-95
references.pmid: 22677184
references.citation: Immunol Rev. 2000 Apr;174:150-9
references.pmid: 10807514
references.citation: Science. 2004 Mar 5;303(5663):1532-5
references.pmid: 15001782
references.citation: Biomed Res Int. 2013;2013:121684
references.pmid: 24171157
references.citation: J Exp Med. 1962 Sep 1;116:381-406
references.pmid: 14467923
references.citation: J Leukoc Biol. 2004 Oct;76(4):854-61
references.pmid: 15258190
references.citation: Annu Rev Immunol. 2005;23:197-223
references.pmid: 15771570
references.citation: Proc Am Thorac Soc. 2004;1(3):239-46
references.pmid: 16113441
references.citation: Cell Tissue Kinet. 1975 Nov;8(6):579-87
references.pmid: 1081432
references.citation: J Neuroimmunol. 2000 Jan 24;102(2):113-24
references.pmid: 10636479
references.citation: J Immunol. 1999 Feb 15;162(4):2368-74
references.pmid: 9973517
references.citation: Proc Natl Acad Sci U S A. 1988 Dec;85(23):9297-301
references.pmid: 2848259
references.citation: J Immunol. 2003 Oct 15;171(8):3970-6
references.pmid: 14530315
references.citation: Neuroimmunomodulation. 2012;19(4):209-19
references.pmid: 22441537
references.citation: Hum Psychopharmacol. 2003 Oct;18(7):507-17
references.pmid: 14533132
references.citation: Infect Immun. 1995 Jun;63(6):2262-8
references.pmid: 7768607
references.citation: Int Immunopharmacol. 2010 Dec;10(12):1573-9
references.pmid: 20951668
references.citation: J Physiol Pharmacol. 1995 Sep;46(3):297-312
references.pmid: 8527811
references.citation: Microbes Infect. 2007 Aug;9(10):1208-15
references.pmid: 17719259
references.citation: Pharmacol Rev. 1974 Sep;26(3):199-288
references.pmid: 4376244
references.citation: Addiction. 2007 Jun;102(6):931-6
references.pmid: 17523988
references.citation: Neuroimmunomodulation. 2009;16(3):191-200
references.pmid: 19246942
references.citation: Blood. 1986 Feb;67(2):257-67
references.pmid: 3002522
references.citation: Life Sci. 2001 Nov 2;69(24):2931-41
references.pmid: 11720096
references.citation: Braz J Med Biol Res. 2011 May;44(5):428-37
references.pmid: 21503414
references.citation: J Anal Toxicol. 2001 Mar;25(2):144-6
references.pmid: 11300507
references.citation: Int Immunopharmacol. 2008 Sep;8(9):1164-71
references.pmid: 18602061
references.citation: J Neuroimmunol. 2002 Apr;125(1-2):94-102
references.pmid: 11960645
references.citation: Cell. 2008 Feb 8;132(3):344-62
references.pmid: 18267068
references.citation: Brain Behav Immun. 2003 Apr;17(2):121-33
references.pmid: 12676574
references.citation: J Physiol Pharmacol. 1991 Mar;42(1):93-103
references.pmid: 1681965
references.citation: Mucosal Immunol. 2010 May;3(3):239-46
references.pmid: 20200511
references.citation: Eur Psychiatry. 2001 Mar;16(2):127-30
references.pmid: 11311178
references.citation: Immunity. 2003 Dec;19(6):891-901
references.pmid: 14670305