Skip to main content

Advertisement

SpringerLink
Log in

Injecting drugs of abuse and immunity: implications for HIV vaccine testing and efficacy

  • Review
  • Published:
Springer Seminars in Immunopathology Aims and scope Submit manuscript

Abstract

The recreational use of legal and illegal drugs has significant effects on immune responses and can potentially modulate susceptibility to infection by a number of pathogens. A number of agents including cannabinoids (marijuana), cocaine opiates, amphetamines, nicotine and alcohol were demonstrated to have potentially adverse effects on the susceptibility to infections, mediated most likely, by adverse effects on immunity. As such, these drugs of abuse could have significant and potentially adverse effects on the vaccination efficacy of a number of vaccines currently on the market and on potential experimental vaccines currently in the pipeline. This review will present an overview on how drugs of abuse potentially impacts immune responses and vaccination efficacy. The emphasis of this review will be the effects of opiate abuse, as exemplified by injecting/intravenous drug users (IDU), on HIV/AIDS and its potential impact on vaccine efficacy trials against this devastating infection/syndrome.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Friedman H, Newton C, Klein TW (2003) Microbial infections, immunomodulation, and drugs of abuse. Clin Microbiol Rev 16:209–219

    Article  PubMed  CAS  Google Scholar 

  2. Friedman H, Pross S, Klein TW (2006) Addictive drugs and their relationship with infectious diseases. FEMS Immunol Med Microbiol 47:330–342

    Article  PubMed  CAS  Google Scholar 

  3. Klein TW, Friedman H, Specter S (1998) Marijuana, immunity and infection. J Neuroimmunol 83:102–115

    Article  PubMed  CAS  Google Scholar 

  4. Mellon RD, Bayer BM (1998) Evidence for central opioid receptors in the immunomodulatory effects of morphine: review of potential mechanism(s) of action. J Neuroimmunol 83:19–28

    Article  PubMed  CAS  Google Scholar 

  5. Nunez-Iglesias MJ, Castro-Bolano C, Losada C, Pereiro-Raposo MD, Riveiro P, Sanchez-Sebio P, Mayan-Santos JM, Rey-Mendez M, Freire-Garabal M (1996) Effects of amphetamine on cell mediated immune response in mice. Life Sci 58:PL29–PL33

    Article  CAS  Google Scholar 

  6. Pellegrino T, Bayer BM (1998) In vivo effects of cocaine on immune cell function. J Neuroimmunol 83:139–147

    Article  PubMed  CAS  Google Scholar 

  7. Yu Q, Zhang D, Walston M, Zhang J, Liu Y, Watson RR (2002) Chronic methamphetamine exposure alters immune function in normal and retrovirus-infected mice. Int Immunopharmacol 2:951–962

    Article  PubMed  CAS  Google Scholar 

  8. Cabral GA, Dove Pettit DA (1998) Drugs and immunity: cannabinoids and their role in decreased resistance to infectious disease. J Neuroimmunol 83:116–123

    Article  PubMed  CAS  Google Scholar 

  9. Gavrilin MA, Mathes LE, Podell M (2002) Methamphetamine enhances cell-associated feline immunodeficiency virus replication in astrocytes. J Neurovirol 8:240–249

    Article  PubMed  CAS  Google Scholar 

  10. Nunez MJ, Fernandez-Rial JC, Couceiro J, Suarez JA, Gomez-Fernandez DE, Rey-Mendez M, Freire-Garabal M (1993) Effects of amphetamine on influenza virus infection in mice. Life Sci 52:PL73–PL78

    Article  PubMed  CAS  Google Scholar 

  11. Risdahl JM, Khanna KV, Peterson PK, Molitor TW (1998) Opiates and infection. J Neuroimmunol 83:4–18

    Article  PubMed  CAS  Google Scholar 

  12. Baldwin GC, Roth MD, Tashkin DP (1998) Acute and chronic effects of cocaine on the immune system and the possible link to AIDS. J Neuroimmunol 83:133–138

    Article  PubMed  CAS  Google Scholar 

  13. Donahoe RM, Vlahov D (1998) Opiates as potential cofactors in progression of HIV-1 infections to AIDS. J Neuroimmunol 83:77–87

    Article  PubMed  CAS  Google Scholar 

  14. Singhal PC, Kapasi AA, Reddy K, Franki N, Gibbons N, Ding G (1999) Morphine promotes apoptosis in Jurkat cells. J Leukoc Biol 66:650–658

    PubMed  CAS  Google Scholar 

  15. Haverkos HW (1991) Infectious diseases and drug abuse. Prevention and treatment in the drug abuse treatment system. J Subst Abuse Treat 8:269–275

    Article  PubMed  CAS  Google Scholar 

  16. CDC fact sheet: drug-associated HIV transmission continues in the United States. (2002) http://www.cdc.gov/hiv/pubs/facts/idu.htm

  17. Cleghorn FR, Blattner WA (1992) Does human T cell lymphotropic virus type I and human immunodeficiency virus type 1 coinfection accelerate acquired immune deficiency syndrome? The jury is still out. Arch Intern Med 152:1372–1373

    Article  PubMed  CAS  Google Scholar 

  18. Gessain A (1996) Epidemiology of HTLV-I and associated diseases. Wiley, New York, pp 33–65

    Google Scholar 

  19. Briggs NC, Battjes RJ, Cantor KP, Blattner WA, Yellin FM, Wilson S, Ritz AL, Weiss SH, Goedert JJ (1995) Seroprevalence of human T cell lymphotropic virus type II infection, with or without human immunodeficiency virus type 1 coinfection, among US intravenous drug users. J Infect Dis 172:51–58

    PubMed  CAS  Google Scholar 

  20. Haverkos HW, Lange WR (1990) From the Alcohol, Drug Abuse, and Mental Health Administration. Serious infections other than human immunodeficiency virus among intravenous drug abusers. J Infect Dis 161:894–902 [published erratum appears in J Infect Dis 1990 Dec; 162(6):1421]

    PubMed  CAS  Google Scholar 

  21. Kaplan MH, Hall WW, Susin M et al (1991) Syndrome of severe skin disease, eosinophilia, and dermatopathic lymphadenopathy in patients with HTLV-II complicating human immunodeficiency virus infection. Am J Med 91:300–309

    Article  PubMed  CAS  Google Scholar 

  22. Tubaro E, Borelli G, Croce C, Cavallo G, Santiangeli C (1993) Effect of morphine on resistance to infection. J Infect Dis 148:656–666

    Google Scholar 

  23. Harrington WJ, Ucar A, Gill PC, Snodgrass S, Sheremata W, Rabin M, Byrne GE, Cabral L, Berger J, Voigt W, Kember R, Miller G, Whitcomb CC, Byrnes JJ, Poiesz B (1995) Clinical spectrum of HTLV-I in South Florida. J Acquir Immune Defic Syndr Human Retrovirol 8:466–473

    Article  Google Scholar 

  24. Murphy EL (1996) The epidemiology of HTLV-I: modes of transmission and their relation to patterns of seroprevalence. Raven Press, New York, pp 295–305

    Google Scholar 

  25. Peterson PK, Molitor TW, Chao CC (1998) The opioid–cytokine connection. J Neuroimmunol 83:63–69

    Article  PubMed  CAS  Google Scholar 

  26. Chao CC, Gekker G, Hu S, Sheng WS, Shark KB, Bu DF, Archer S, Bidlack JM, Peterson PK (1996) kappa opioid receptors in human microglia downregulate human immunodeficiency virus 1 expression. Proc Natl Acad Sci USA 93:8051–8056

    Article  PubMed  CAS  Google Scholar 

  27. Virsik PA, Bussiere JL (1995) Adjuvant effects on morphine-induced suppression of immune responses to MN rgp120/HIV-1 in mice. Adv Exp Med Biol 373:183–188

    PubMed  CAS  Google Scholar 

  28. Sharp BM, Roy S, Bidlack JM (1998) Evidence for opioid receptors on cells involved in host defense and the immune system. J Neuroimmunol 83:45–56

    Article  PubMed  CAS  Google Scholar 

  29. Sharp BM, Gekker G, Li MD, Chao CC, Peterson PK (1998) Delta-Opioid suppression of human immunodeficiency virus-1 expression in T cells (Jurkat). Biochem Pharmacol 56:289–292

    Article  PubMed  CAS  Google Scholar 

  30. Madden JJ, Whaley WL, Ketelsen D (1998) Opiate binding sites in the cellular immune system: expression and regulation. J Neuroimmunol 83:57–62

    Article  PubMed  CAS  Google Scholar 

  31. Adler MW, Geller EB, Rogers TJ, Henderson EE, Eisenstein TK (1993) Opioids, receptors, and immunity. Adv Exp Med Biol 335:13–20

    PubMed  CAS  Google Scholar 

  32. Starec M, Sinet M, Kodym P, Rosina J, Fiserova A, Desforges B, Rouveix B (1997) The effect of drugs on the mortality of mice inoculated with Friend leukaemia virus or toxoplasma gondii. Physiol Res 46:107–111

    PubMed  CAS  Google Scholar 

  33. Rouveix B (1992) Opiates and immune function: consequences on infectious diseases with special references to AIDS. Therapie 47:503–512

    PubMed  CAS  Google Scholar 

  34. Peterson PK, Sharp BM, Gekker G, Portoghese PS, Sannerud K, Balfour HH Jr (1990) Morphine promotes the growth of HIV-1 in human peripheral blood mononuclear cell cocultures. AIDS 4:869–873

    Article  PubMed  CAS  Google Scholar 

  35. Peterson PK, Gekker G, Hu S, Anderson WR, Kravitz F, Portoghese PS, Balfour HH Jr, Chao CC (1994) Morphine amplifies HIV-1 expression in chronically infected promonocytes cocultured with human brain cells. J Neuroimmunol 50:167–175

    Article  PubMed  CAS  Google Scholar 

  36. Chuang LF, Killam KG, Chuang RY (1993) Increased replication of simian immunodeficiency virus in CEM x174 cells by morphine sulfate. Biochem Biophys Res Commun 195:1165–1173

    Article  PubMed  CAS  Google Scholar 

  37. Bidlack JM, Saripalli LD, Lawrence DM (1992) kappa-Opioid binding sites on a murine lymphoma cell line. Eur J Pharmacol 227:257–265

    Article  PubMed  CAS  Google Scholar 

  38. Chao CC, Hu S, Shark KB, Sheng WS, Gekker G, Peterson PK (1997) Activation of mu opioid receptors inhibits microglial cell chemotaxis. J Pharmacol Exp Ther 281:998–1004

    PubMed  CAS  Google Scholar 

  39. Carr DJ, Carpenter GW, Garza HH Jr, France CP, Prakash OM (1995) Chronic & infrequent opioid exposure suppresses IL-2R expression on rhesus monkey peripheral blood mononuclear cells following stimulation with pokeweed mitogen. Int J Neurosci 81:137–148

    Article  PubMed  CAS  Google Scholar 

  40. Roy S, Chapin RB, Cain KJ, Charboneau RG, Ramakrishnan S, Barke RA (1997) Morphine inhibits transcriptional activation of IL-2 in mouse thymocytes. Cell Immunol 179:1–9

    Article  PubMed  CAS  Google Scholar 

  41. Carr DJ, France CP (1993) Immune alterations in morphine treated rhesus monkeys. J Pharmacol Exp Ther 267:9–15

    PubMed  CAS  Google Scholar 

  42. Gungor M, Genc E, Sagduyu H, Eroglu L, Koyuncuoglu H (1980) Effect of chronic administration of morphine on primary immune responses in mice. Experientia 36:1309–1310

    Article  PubMed  CAS  Google Scholar 

  43. Watson RR, Nguyen TH (1990) Suppression by morphine and ethanol of tumor cell cytotoxic activity released by macrophages from retrovirally infected mice upon in vitro stimulation by beta carotene. Prog Clin Biol Res 325:79–91

    PubMed  CAS  Google Scholar 

  44. Beilke MA, Japa S, Vinson DG (1998) HTLV-I and HTLV-II virus expression increase with HIV-1 coinfection. J Acquir Immune Defic Syndr Human Retrovirol 17:391–397

    CAS  Google Scholar 

  45. Bartholomew C, Blattner W, Cleghorn F (1987) Progression to AIDS in homosexual men co-infected with HIV and HTLV-I in Trinidad. Lancet 19:1469

    Article  Google Scholar 

  46. Wiktor SZ, Cannon RO, Atkinson WL et al (1992) Infection with human T lymphotropic virus type I and II in sexually transmitted diseases clinics in Baltimore and New Orleans. J Infect Dis 165:920–924

    PubMed  CAS  Google Scholar 

  47. MacFarlane AS, Peng X, Meissler JJ Jr, Rogers TJ, Geller EB, Adler MW, Eisenstein TK (2000) Morphine increases susceptibility to oral Salmonella typhimurium infection. J Infect Dis 181:1350–1358

    Article  PubMed  CAS  Google Scholar 

  48. Peterson PK, Molitor TW, Chao CC, Sharp B (1990) Opiates and cell mediated immunity. In: Watson RR (ed) Drugs of abuse and immune function. CRC Press, Boca Raton

    Google Scholar 

  49. Sacerdote P, Manfredi B, Mantegazza P, Panerai AE (1997) Antinoceptive and immunosuppressive effects of opiate drugs: a structure-related activity study. Br J Pharmacol 121:834–840

    Article  PubMed  CAS  Google Scholar 

  50. Stefano GB, Leung MK, Bilfinger TV, Scharrer B (1995) Effect of prolonged exposure to morphine on responsiveness of human and invertebrate immunocytes to stimulatory molecules. J Neuroimmunol 63:175–181

    Article  PubMed  CAS  Google Scholar 

  51. Bhargava HN, Thomas PT, Thorat S, House RV (1994) Effects of morphine tolerance and abstinence on cellular immune function. Brain Res 642:1–10

    Article  PubMed  CAS  Google Scholar 

  52. Shavit Y, Lewis JS, Terman GW, Gale RP, Liebeskind JC (1984) Opioid peptides mediate the suppressive effect of stress on natural killer cell cytotoxicity. Science 223:188–190

    Article  PubMed  CAS  Google Scholar 

  53. Colacchio TA, Yeager MP, Hildebrandt LW (1994) Perioperative immunomodulation in cancer surgery. Am J Surg 167:174–179

    Article  PubMed  CAS  Google Scholar 

  54. Yeager MP, Colacchio TA, Yu CT, Hildebrandt L, Howell AL, Weiss J, Guyre PM (1995) Morphine inhibits spontaneous and cytokine-enhanced natural killer cell cytotoxicity. Anesthesiology 83:500–508

    Article  PubMed  CAS  Google Scholar 

  55. Eisenstein TK, Meissler JJ Jr, Geller EB, Adler MW (1990) Immunosuppression to tetanus toxoid induced by implanted morphine pellets. Ann N Y Acad Sci 594:377

    Article  Google Scholar 

  56. Louwagie J, McCutchan F, Mascola J (1993) Genetic subtypes of HIV-1. AIDS Res Hum Retrovir 9:147–153

    Article  Google Scholar 

  57. Beilke MA, Greenspan DL, Impey A (1994) Laboratory study of HIV-1 and HTLV-I/II coinfection. J Med Virol 44:132–143

    Article  PubMed  CAS  Google Scholar 

  58. Agadjanyan MG, Ugen KE, Wang B, Williams WV, Weiner DB (1994) Identification of an 80-kilodalton membrane glycoprotein important for human T-cell leukemia virus type I and type II syncytium formation and infection. J Virol 68:485–493

    PubMed  CAS  Google Scholar 

  59. Schwebke J, Calsyn D, Shriver K et al (1994) Prevalence and epidemiological correlates of human T cell lymphotropic virus infection among intravenous drug users. J Infect Dis 169:962–967

    PubMed  CAS  Google Scholar 

  60. Nyland SB, Cao C, Bai Y, Loughran TP, Ugen KE (2003) Modulation of infection and type 1 cytokine expression parameters by morphine during in vitro coinfection with human T-cell leukemia virus type I and HIV-1. J Acquir Immune Defic Syndr 32:406–416

    Article  PubMed  CAS  Google Scholar 

  61. Klimas NG, Page JB, Patarca R, Chitwood D, Morgan R, Fletcher MA (1993) Effects of retroviral infections on immune function in African–American intravenous drug users. AIDS 7:331–335

    Article  PubMed  CAS  Google Scholar 

  62. Good L, Maggirwar SB, Sun SC (1996) Activation of the IL-2 gene promoter by HTLV-I tax involves induction of NF-AT complexes bound to the CD28-responsive element. EMBO J 15:3744–3750

    PubMed  CAS  Google Scholar 

  63. Grimm MC, Ben-Baruch A, Taub DD, Howard OM, Resau JH, Wang JM, Ali H, Richardson R, Snyderman R, Oppenheim JJ (1998) Opiates transdeactivate chemokine receptors: delta and mu opiate receptor-mediated heterologous desensitization. J Exp Med 188:317–325

    Article  PubMed  CAS  Google Scholar 

  64. Grimm MC, Ben-Baruch A, Taub DD, Howard OMZ, Wang JM, Oppenheim JJ (1998) Opiate inhibition of chemokine-induced chemotaxis. Ann N Y Acad Sci 840:9–20

    Article  PubMed  CAS  Google Scholar 

  65. Wetzel MA, Steele AD, Eisenstein TK, Adler MW, Henderson EE, Rogers TJ (2000) Mu-opioid induction of monocyte chemoattractant protein-1, RANTES, and IFN-gamma-inducible protein-10 expression in human peripheral blood mononuclear cells. J Immunol 165:6519–6524

    PubMed  CAS  Google Scholar 

  66. Quan VM, Chung A, Long HT, Dondero TJ (2000) HIV in Vietnam: the evolving epidemic and the prevention response, 1996 through 1999. J Acquir Immune Defic Syndr 25:360–369

    Article  PubMed  CAS  Google Scholar 

  67. Beyrer C (2002) Injecting drug users and HIV vaccine trials : what does the science say? IAVI Report 6(3)

  68. Benson J, Chougnet C, Robert-Guroff M, Montefiori D, Markham P, Shearer G, Gallo RC, Cranage M, Paoletti E, Limbach K, Venzon D, Tartaglia J, Franchini G (1998) Recombinant vaccine-induced protection against the highly pathogenic simian immunodeficiency virus SIV(mac251): dependence on route of challenge exposure. J Virol 72:4170–4182

    PubMed  CAS  Google Scholar 

  69. Mascola JR (2002) Passive transfer studies to elucidate the role of antibody-mediated protection against HIV-1. Vaccine 20:1922–1925

    Article  PubMed  CAS  Google Scholar 

  70. Vanichseni S, Kitayaporn D, Mastro TD, Mock PA, Raktham S, Des Jarlais DC, Sujarita S, Srisuwanvilai LO, Young NL, Wasi C, Subbarao S, Heyward WL, Esparza L, Choopanya K (2001) Continued high HIV-1 incidence in a vaccine trial preparatory cohort of injection drug users in Bangkok, Thailand. AIDS 15:397–405

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, FL, 33612, USA

    Kenneth E. Ugen

  2. Center for Molecular Delivery, College of Medicine, University of South Florida, Tampa, FL, 33612, USA

    Kenneth E. Ugen

  3. College of Medicine, Penn State Cancer Institute, Pennsylvania State University, Hershey, PA, 17033, USA

    Susan B. Nyland

Authors
  1. Kenneth E. Ugen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan B. Nyland
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenneth E. Ugen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ugen, K.E., Nyland, S.B. Injecting drugs of abuse and immunity: implications for HIV vaccine testing and efficacy. Springer Semin Immun 28, 281–287 (2006). https://doi.org/10.1007/s00281-006-0045-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00281-006-0045-0

Keywords

Search

Navigation