title: Heroin use is associated with suppressed pro-inflammatory cytokine response after LPS exposure in HIV-infected individuals.
abstract: BACKGROUND
  Opioid use is associated with increased incidence of infectious diseases. Although experimental studies have shown that opioids affect various functions of immune cells, only limited data are available from human studies. Drug use is an important risk factor for HIV transmission; however no data are available whether heroin and/or methadone modulate immune response. Therefore, we examined the effect of heroin and methadone use among HIV-infected individuals on the production of cytokines after ex vivo stimulation with various pathogens.
  
  
  METHODS
  Treatment naïve HIV-infected individuals from Indonesia were recruited. Several cohorts of individuals were recruited: 1) using heroin 2) receiving methadone opioid substitution 3) using heroin over 1 year ago and 4) controls (never used opioids). Whole blood was stimulated with Mycobacterium tuberculosis, Candida albicans and LPS for 24 to 48 hours. Cytokine production (IL-1 β, IL-6, IL-10, IFN-α, IFN-γ and TNF-α) was determined using multiplex beads assay.
  
  
  RESULTS
  Among 82 individuals, the cytokine levels in unstimulated samples did not differ between groups. Overall, heroin users had significantly lower cytokine response after exposure to LPS (p<0.05). After stimulation with either M. tuberculosis or C. albicans the cytokine production of all groups were comparable.
  
  
  CONCLUSIONS
  The cytokine production after exposure to LPS is significantly down-regulated in HIV-infected heroin users. Interesting, methadone use did not suppress cytokine response, which could have implications guidelines of opioid substitution.
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Hinta
authors.initials: H
authors.lastname: Meijerink
authors.affiliation: Health Research Unit, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Bandung, Indonesia.
authors.forename: Agnes
authors.initials: A
authors.lastname: Indrati
authors.affiliation: Health Research Unit, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Bandung, Indonesia.
authors.forename: Fitri
authors.initials: F
authors.lastname: Utami
authors.affiliation: Health Research Unit, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Bandung, Indonesia.
authors.forename: Suharyani
authors.initials: S
authors.lastname: Soedarmo
authors.affiliation: Health Research Unit, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Bandung, Indonesia.
authors.forename: Bachti
authors.initials: B
authors.lastname: Alisjahbana
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Mihai G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Reinout
authors.initials: R
authors.lastname: van Crevel
authors.affiliation: Health Research Unit, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital, Bandung, Indonesia.
authors.forename: Rudi
authors.initials: R
authors.lastname: Wisaksana
authors.affiliation: Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Andre Jam
authors.initials: AJ
authors.lastname: van der Ven
mesh_terms: D000328:Adult; D016207:Cytokines / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000276:immunology*; D006556:Heroin Dependence / Q000097:blood / Q000276:immunology*; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D055815:Young Adult
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides
references.citation: Clin Infect Dis. 2009 Nov 15;49(10):1605-15
references.pmid: 19842982
references.citation: AIDS. 2010 Jul 31;24(12):1857-65
references.pmid: 20479633
references.citation: Addiction. 2010 Jun;105(6):1055-61
references.pmid: 20331555
references.citation: Neurosci Lett. 2011 Feb 1;489(1):43-7
references.pmid: 21130144
references.citation: J Biol Chem. 2011 Mar 25;286(12):10225-32
references.pmid: 21245149
references.citation: J Neuroimmune Pharmacol. 2011 Dec;6(4):442-65
references.pmid: 21789507
references.citation: Brain Behav Immun. 2012 Mar;26(3):480-8
references.pmid: 22240038
references.citation: J Cell Physiol. 2012 Jul;227(7):2832-41
references.pmid: 22034138
references.citation: Proc Natl Acad Sci U S A. 2012 Apr 17;109(16):6325-30
references.pmid: 22474354
references.citation: J Neurosci. 2013 Jan 16;33(3):961-71
references.pmid: 23325235
references.citation: PLoS One. 2013;8(1):e54040
references.pmid: 23349783
references.citation: Br J Pharmacol. 2013 Mar;168(6):1421-9
references.pmid: 23083095
references.citation: Biol Psychiatry. 2013 Apr 15;73(8):729-37
references.pmid: 23384483
references.citation: Acta Oncol. 2013 Jun;52(5):1022-33
references.pmid: 23145506
references.citation: Anesth Analg. 2000 Jun;90(6):1411-4
references.pmid: 10825330
references.citation: J Viral Hepat. 2000 Jul;7(4):302-8
references.pmid: 10886541
references.citation: Vaccine. 2000 Dec 8;19(9-10):1113-7
references.pmid: 11137246
references.citation: Arch Intern Med. 2002 Oct 14;162(18):2125-32
references.pmid: 12374521
references.citation: J Acquir Immune Defic Syndr. 2002 Oct 1;31 Suppl 2:S62-9
references.pmid: 12394784
references.citation: Virology. 2003 Apr 25;309(1):99-107
references.pmid: 12726730
references.citation: Life Sci. 2003 Aug 29;73(15):1873-93
references.pmid: 12899914
references.citation: Anesth Analg. 2003 Sep;97(3):822-7
references.pmid: 12933409
references.citation: HIV Clin Trials. 2004 May-Jun;5(3):125-31
references.pmid: 15248136
references.citation: J Anesth. 2004;18(3):190-5
references.pmid: 15290418
references.citation: J Immunol. 1983 Apr;130(4):1658-62
references.pmid: 6300232
references.citation: J Immunol. 1986 Feb 1;136(3):934-9
references.pmid: 2934481
references.citation: Anaesth Intensive Care. 1987 Feb;15(1):27-37
references.pmid: 3032015
references.citation: J Clin Invest. 1987 Sep;80(3):824-31
references.pmid: 3040807
references.citation: Immunopharmacology. 1987 Oct-Nov;14(2):93-9
references.pmid: 2448267
references.citation: J Neuroimmunol. 1992 Aug;39(3):219-30
references.pmid: 1644897
references.citation: Ann Surg. 1993 Mar;217(3):286-92
references.pmid: 8452407
references.citation: Int J Immunopharmacol. 1993 Apr;15(3):447-53
references.pmid: 8389331
references.citation: J Pharmacol Exp Ther. 1993 Jun;265(3):1071-8
references.pmid: 7685383
references.citation: Brain Res. 1994 Apr 11;642(1-2):1-10
references.pmid: 8032870
references.citation: Neurochem Int. 1994 May;24(5):401-26
references.pmid: 7647696
references.citation: Anesthesiology. 1995 Sep;83(3):500-8
references.pmid: 7661350
references.citation: AIDS. 1998 Mar 5;12(4):381-8
references.pmid: 9520167
references.citation: J Neuroimmunol. 1998 Mar 15;83(1-2):77-87
references.pmid: 9610676
references.citation: Ann Surg. 1998 Aug;228(2):188-93
references.pmid: 9712563
references.citation: Psychopharmacology (Berl). 2005 May;179(3):700-4
references.pmid: 15806416
references.citation: Biochem Biophys Res Commun. 2005 Aug 12;333(4):1295-9
references.pmid: 15979578
references.citation: Neurosci Behav Physiol. 2009 Jul;39(6):591-5
references.pmid: 19513849
references.citation: Shock. 2013 Dec;40(6):451-62
references.pmid: 23989337
references.citation: J Int AIDS Soc. 2014;17:18844
references.pmid: 24388495
references.citation: Mol Pain. 2014;10:10
references.pmid: 24499354
references.citation: PLoS One. 2014;9(5):e97361
references.pmid: 24824631
references.citation: J Interferon Cytokine Res. 2014 Nov;34(11):885-93
references.pmid: 24955730
references.citation: AIDS. 2015 Jan 28;29(3):385-8
references.pmid: 25834861
references.citation: J Neurosci. 2012 Jul 18;32(29):9917-30
references.pmid: 22815507
references.citation: Clin Infect Dis. 2005 Sep 15;41(6):906-11
references.pmid: 16107994
references.citation: Clin Infect Dis. 2005 Oct 1;41(7):1027-34
references.pmid: 16142670
references.citation: J Clin Anesth. 2005 Dec;17(8):575-80
references.pmid: 16427525
references.citation: Clin Chim Acta. 2006 Jul 15;369(1):40-5
references.pmid: 16487501
references.citation: FEMS Immunol Med Microbiol. 2006 Aug;47(3):330-42
references.pmid: 16872369
references.citation: Nature. 2007 Jun 21;447(7147):972-8
references.pmid: 17538624
references.citation: Prog Brain Res. 2007;163:245-63
references.pmid: 17765723
references.citation: Eur Cytokine Netw. 2007 Dec;18(4):210-4
references.pmid: 17993452
references.citation: Anesth Analg. 2008 Apr;106(4):1142-9, table of contents
references.pmid: 18349186
references.citation: Cell Immunol. 2008 Mar-Apr;252(1-2):146-54
references.pmid: 18279847
references.citation: Arch Immunol Ther Exp (Warsz). 2008 Sep-Oct;56(5):299-309
references.pmid: 18836861
references.citation: Drug Alcohol Depend. 2009 Jan 1;99(1-3):183-92
references.pmid: 18823721
references.citation: Trends Immunol. 2009 Oct;30(10):475-87
references.pmid: 19781994
references.citation: J Immunol. 2013 Sep 15;191(6):3400-9
references.pmid: 23960234
references.citation: J Neurosci. 2013 Oct 2;33(40):15952-63
references.pmid: 24089500
references.citation: J Acquir Immune Defic Syndr. 2013 Dec 15;64(5):425-33
references.pmid: 23797689