In a previous study, the authors have shown that herpes simplex virus type 1 (HSV-1) glycoprotein B DNA vaccine but not live vaccine (non-virulent KOS strain) failed to induce protective immunity against acute HSV-1 challenge in morphine-dependent mice. The present study reports the effect of morphine withdrawal on protective immunity induced by live HSV-1 immunization. BALB/c mice were vaccinated with KOS strain as a live vaccine. Three weeks later, they were exposed to morphine for 14 days. On day 14, withdrawal was induced by administration of normal saline instead of morphine. One day later, immune responses against HSV-1 were assessed by measuring cytotoxicity, lymphocyte proliferation and interferon-γ production. Protection against HSV-1 was assessed by measuring the mortality rate after acute HSV-1 challenge. The results showed that withdrawal from morphine reduces protective immunity against acute HSV-1 challenge. These findings raise the possibility that withdrawal from morphine may increase the susceptibility of drug addicts to infectious diseases.

1.
Friedman H, Newton C, Klein TW: Microbial infections, immunomodulation, and drugs of abuse. Clin Microbiol Rev 2003;16:209–219.
2.
McCarthy L, Wetzel M, Sliker JK, Eisenstein TK, Rogers TJ: Opioids, opioid receptors, and the immune response. Drug Alcohol Depend 2001;62:111–123.
3.
Eisenstein TK, Rahim RT, Feng P, Thingalaya NK, Meissler JJ: Effects of opioid tolerance and withdrawal on the immune system. J Neuroimmune Pharmacol 2006;1:237–249.
4.
Govitrapong P, Suttitum T, Kotchabhakdi N, Uneklabh T: Alterations of immune functions in heroin addicts and heroin withdrawal subjects. J Pharmacol Exp Ther 1998;286:883–889.
5.
Rahim RT, Meissler JJ, Zhang L, Adler MW, Rogers TJ, Eisenstein TK: Withdrawal from morphine in mice suppresses splenic macrophage function, cytokine production, and costimulatory molecules. J Neuroimmunol 2003;144:16–27.
6.
Donahoe RM, Byrd LD, McClure HM, Fultz P, Brantley M, Marsteller F, Ansari AA, Wenzel D, Aceto M: Consequences of opiate-dependency in a monkey model of AIDS. Adv Exp Med Biol 1993;335:21–28.
7.
Feng P, Meissler JJ Jr, Adler MW, Eisenstein TK: Morphine withdrawal sensitizes mice to lipopolysaccharide: elevated TNF-alpha and nitric oxide with decreased IL-12. J Neuroimmunol 2005;164:57–65.
8.
Feng P, Wilson QM, Meissler JJ Jr, Adler MW, Eisenstein TK: Increased sensitivity to Salmonella enterica Serovar typhimurium infection in mice undergoing withdrawal from morphine is associated with suppression of interleukin-12. Infect Immun 2005;73:7953–7959.
9.
Whitley RJ, Roizman B: Herpes simplex virus infections. Lancet 2001;357:1513–1518.
10.
Jamali A, Roostaee MH, Soleimanjahi H, Ghaderi Pakdel F, Bamdad T: DNA vaccine-encoded glycoprotein B of HSV-1 fails to protect chronic morphine-treated mice against HSV-1 challenge. Comp Immunol Microbiol Infect Dis 2007;30:71–80.
11.
Soleimanjahi H, Roostaee MH, Rasaee MJ, Mahboudi F, Kazemnejad A, Bamdad T, Zandi K: The effect of DNA priming-protein boosting on enhancing humoral immunity and protecting mice against lethal HSV infections. FEMS Immunol Med Microbiol 2006;46:100–106.
12.
Carpenter GW, Carr DJ: Pretreatment with beta-funaltrexamine blocks morphine-mediated suppression of CTL activity in alloimmunized mice. Immunopharmacology 1995;29:129–140.
13.
Osorio Y, Ghiasi H: Comparison of adjuvant efficacy of herpes simplex virus type 1 recombinant viruses expressing TH1 and TH2 cytokine genes. J Virol 2003;77:5774–5783.
14.
Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55–63.
15.
Koelle DM, Corey L: Recent progress in herpes simplex virus immunobiology and vaccine research. Clin Microbiol Rev 2003;16:96–113.
16.
Bhargava HN, Thomas PT, Thorat S, House RV: Effects of morphine tolerance and abstinence on cellular immune function. Brain Res 1994;642:1–10.
17.
Weed MR, Carruth LM, Adams RJ, Ator NA, Hienz RD: Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques. J Neuroimmune Pharmacol 2006;1:250–259.
18.
Kelschenbach J, Barke RA, Roy S: Morphine withdrawal contributes to Th cell differentiation by biasing cells toward the Th2 lineage. J Immunol 2005;175:2655–2665.
19.
Kelschenbach J, Ninkovic J, Wang J, Krishnan A, Charboneau R, Barke RA, Roy S: Morphine withdrawal inhibits IL-12 induction in a macrophage cell line through a mechanism that involves cAMP. J Immunol 2008;180:3670–3679.
20.
Halford WP, Balliet JW, Gebhardt BM: Re-evaluating natural resistance to herpes simplex virus type 1. J Virol 2004;78:10086–10095.
21.
Nass PH, Elkins KL, Weir JP: Protective immunity against herpes simplex virus generated by DNA vaccination compared to natural infection. Vaccine 2001;19:1538–1546.
22.
Holterman AX, Rogers K, Edelmann K, Koelle DM, Corey L, Wilson CB: An important role for major histocompatibility complex class I-restricted t cells, and a limited role for gamma interferon, in protection of mice against lethal herpes simplex virus infection. J Virol 1999;73:2058–2063.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.