Drugs of Abuse, Immunomodulation, and Aids

314 Pages·1998·12.81 MB·English

by  Sulie L. Chang

DRUGS OF ABUSE,
IMMUNOMODULATION,
AND AIDS
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University oj New York at BuJJalo
IRUN R. COHEN, The Weizmann Institute oj Science
DAVID KRITCHEVSKY, Wistar Institute
ABEL LAJTHA, N. S. Kline Institute Jar Psychiatric Research
RODOLFO PAOLETTI, University oj Milan
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DRUGS OF ABUSE, IMMUNOMODULATION, AND AIDS
Edited by Herman Friedman, John J. Madden, and Thomas W. Klein
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DRUGS OF ABUSE,
IMMUNOMODULATION,
ANDAIDS
Edited by
Herman Friedman
University of South Florida College of Medicine
Tampa, Florida
John J. Madden
Emory University
Atlanta, Georgia
and
Thomas W. Klein
University of South Florida College of Medicine
Tampa, Florida
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
Lltn. .. r." of Congress Cataloglng-ln-Publlcatlon Data
Drugs of abuse, lmmunumodulatlon, and AIDS / edlted by Herman
Frledman, John J. Madden, and Thomas W. Klein.
p. cm. -- (Advances In experimental medlclne and blology ; v.
437>
"Proceedlngs of the Flfth Annual Symposium on Drugs of Abuse,
Immunomodulatlon, and AIDS, held June 12-14, 1997, In Nashville,
Tennessee"--T.p. verso.
Includes bib11ogra~~llcai r~f~rerlces arid tlldex.
ISBN 978-1-4613-7439-8 ISBN 978-1-4615-5347-2 (eBook)
DOI 10.1007/978-1-4615-5347-2
1. Immunosuppresslon--Congresses. 2. Drugs of abuse
-Pathophyslology--Congresses. 3. AIDS (Dlsease)--Pathophysiology-
-Congresses. I. Frledman, Herman, 1931- 11. Klein, Thomas W.
111. Symposium on Drugs of Abuse, Immunomodulatlon, and AIDS (5th
1997 , Nashville, Tenn.) IV. Series.
[DNLM, 1. Street Drugs--lmmunology congresses. 2. Acquired
Immunodeflclency Syndrome--lmmunology congresses. 3. Immune System
-drug effects congresses. 4. Nervous System--drug effects
congresses. W1 AD559 v.437 19981
QR188.45.D78 1998
616.07'9--dc21
DNLM/DLC
for Llbrary of Congress 98-18199
CIP
Proceedings ofthe Fifth Annual Symposium on Drugs of Abuse, Immunomodulation, and AIDS,
held lune 12-14, 1997, in Nashville, Tennessee
ISBN 978-1-4613-7439-8
© 1998 Springer Science+Business Media New York
Originally published by Plenum Press, New York in 1998
Softcover reprint ofthe hardcover 1st edition
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PREFACE
Introduction and Perspectives
This volume represents the Proceedings of the Fifth Annual Symposium on Drugs of
Abuse, Immunomodulation, and AIDS. The meeting was held in Nashville, Tennessee, June
12-14, 1997. In this symposium, as in the past, newer knowledge was reviewed concerning
the relationship between the immune and the nervous systems with regard to the effects of
drugs of abuse. This symposium focused on the relationship between the immune system
and the nervous system with regard to the effects of drugs of abuse and infections such as
the immunodeficiency virus that causes AIDS. As in the past symposia, presentations fo
cused on the brain-immune axis from the viewpoint of drugs of abuse rather than from the
subject of the brain or immunity alone. The aim of this series of conferences has been to
clarify the consequences ofimmunomodulation induced by drugs of abuse on susceptibility
and pathogenesis of infectious diseases, both in man and in various animal model systems.
Recreational use of drugs of abuse, such as morphine, cocaine, and marijuana, as well
as alcohol, by large numbers of individuals in this country and around the world has
aroused serious concerns about the consequences of use of such drugs, especially on the
normal physiological responses of an individual, including immune mechanisms. It is now
widely known that many drugs of abuse, including marijuana, are used by millions ofindi
viduals in this country and by even more abroad. Use of cocaine, especially crack cocaine,
is now considered to be epidemic in this country. Alcoholism is also considered a major
problem worldwide as well as in this country, and it has been estimated there are more than
10,000,000 alcoholics in the United States alone. A significant portion of those individuals
hospitalized for infectious diseases are known to be alcoholics. Recently there have been
reports of an association between drugs such as marijuana and malignancy. These observa
tions have encouraged continued laboratory studies aimed at determining the nature and
mechanism of how such drugs of abuse affect the immune response system as well as the
neuroendocrine and neurological systems in general that, in turn, affect immunity.
Much data have now accumulated showing that drugs of abuse can markedly alter
the immune response in human populations as well as in experimental animals, both in
vivo and in vitro. Furthermore, studies on microbial infection have shown that many drugs
of abuse are often associated with increased susceptibility to infectious diseases, espe
cially opportunistic intracellular microbial infections, including infections by the AIDS
virus. Furthermore, the mechanisms whereby drugs of abuse increase the likelihood of in
fection in humans as well as experimental animals by opportunistic infections have begun
v
vi Preface
to be delineated. In particular, it is now known that drugs such as morphine, marijuana,
and cocaine, as well as alcohol, enhance the susceptibility of humans as well as animals to
infections by bacteria, viruses, protozoa, or fungi. Recently, a number of experimental
studies with lymphoid cells from animals or man challenged in vitro with infectious agents
have shown that drugs of abuse increased their susceptibility. There have also now been a
number of laboratory studies showing the possible relationship of effects on signal
transduction mechanisms by drugs of abuse and correlative increased susceptibility of the
cells to infectious agents.
Many investigators believe it is appropriate to focus attention now on the accumulat
ing new information concerning the effects of recreational drugs of abuse and modulation
of the immune response, especially that pertaining to resistance mechanisms important in
infections, as well as resistance to malignancy and alteration or frequency of autoimmune
diseases. Many investigators also believe that studies concerning how illicit drugs of abuse
affect immunity are even more urgent at the present time because of the worldwide
epidemic of AIDS, which is caused by the human immunodeficiency virus resulting in a
collapse of the immune system, making an individual susceptible to opportunistic microbial
infections that otherwise would not cause disease in healthy individuals. Among the
possible mechanisms involved are the effects of these drugs of abuse on the brain-immune
axis. The brain-immune axis is known to be highly complex and evinces highly dynamic
interactions. The effect of various drugs of abuse on the interactive system between the
nervous and immune systems has multiple consequences, depending upon the specific sites
of action of a drug, duration of exposure, and underlying neurological and behavioral status
of the exposed individual to the drug. Furthermore, the understanding of the effects of a
drug of abuse and the immune system, as well as the neuroimmune axis and neuroendocrine
systems in general, involves many interdisciplinary areas, such as behavioral, pharma
cological, neurological, anatomical, and cellular and molecular studies. Thus it is necessary
to elucidate the interactions of drugs of abuse with the brain-immune axis.
The first part of the symposium on which this volume is based is concerned mainly
with opiates and their effects on both the neuroendocrine and the immune systems. Infec
tious diseases that are accelerated by opiates have been experimentally investigated in de
tail. There is now much information indicating that morphine as well as other opiates
accelerate the susceptibility to infection by viruses as well as opportunistic bacteria. The
effect of morphine on immune cells, including macrophages, is being examined by a rela
tively large number of laboratories. The effect of morphine and other opiates on metabolic
function of neurological and immune cells has been also recently investigated. The effect of
opiates on signal transduction as well as opiate receptors on immune cells is being investi
gated in a number oflaboratories. There were valuable observations presented at this meet
ing concerning opiate receptors on immune and neurological cells. Several papers were
presented concerning cocaine as related to Th I and Th2 helper cells and also the effect of
cocaine on AIDS dementia and vasculitis. Several presentations reviewed the effects of
marijuana, especially its major psychoactive component tetrahydrocannabinol, on cytokines
and especially the involvement of the cannabinoid receptors. Newer information concern
ing marijuana effects on the central nervous system induced by cytokine effects was
described. Presentations were also made concerning alcohol effects on immunity as well as
other drugs, including isobutyl nitrite, norepinephrine, and nicotine as well as methionine
enkephalin. The reasons for the apparent disparity between basic science studies relating
effects on immunity and epidemiological studies concerning AIDS progression and drugs of
abuse were discussed at the meeting. Most immunological studies in animals and in vitro
have in the past proven predictive for effects of drugs of abuse on the immune response in
Preface vii
humans. For example, it is now accepted that animal experiments show conclusively thaI
opiates and other drugs of abuse can indeed affect the immune response. Some studies in
vitro have shown there is an acceleration of HIV replication and acceleration of AIDS-like
virus-induced disease in animals. Many investigators believe it is logical that drugs of
abuse can affect humans as well as animals to show higher susceptibility to the AIDS virus.
Basic scientists, especially in the area of pharmacology, have always been concerned with
the role of drug interactions, dose responses, pharmokinetics, frequency and duration of
drug doses, and similar factors. Many basic scientists believe that epidemiological studies
concerning drugs of abuse and AIDS must take into consideration such factors and should
acknowledge that drug abusers are usually polydrug users. The subjects being studied in
terms of AIDS and drugs of abuse should be investigated in terms of duration of drug use,
route of drug use such as injection versus oral use, the type of drugs being used, dosages,
etc. It is apparent that the design of various studies by biomedical and clinical scientists and
the questions they ask must also take into consideration these variables and should be an
swered by acceptable research designs and statistical procedures. Epidemiological studies
should take into account variations among populations and the design of the questions be
ing asked as well as many other variables. Although it appears that there is disagreement
between basic scientists and epidemiologists concerning the potential of drugs of abuse to
exacerbate the progression of HIV infection, it is felt this disagreement is resolvable
through proper collaboration and experimental design.
It is the hope of the organizers of this series of conferences, including the conference
in Nashville on which this proceeding is based, that the publication of the proceedings will
further inspire interest in this rapidly developing field of basic medical science in terms of
immune modulation, AIDS, and drugs of abuse. This publication, we hope, will further the
understanding of newer knowledge concerning the impact of drugs of abuse on the brain
immune axis and its relationship to immunodeficiency, especially that caused by the AIDS
virus. We also thank the organizing committee and its administrator, Ms. Suzanne Ingalls,
for invaluable assistance that contributed to the success of the symposium. The editors of
this volume also thank Mrs. Ilona Friedman for invaluable assistance as editorial coordina
tor and managing editor for this volume of the symposium proceedings. We also thank the
National Institute on Drug Abuse for financial support and especially Dr. Charles Sharp,
project director ofNIDA for Immunology, for continuing interest and invaluable assistance.
H. Friedman
1. 1. Madden
T. W. Klein
November 1997
DRUGS OF ABUSE, IMMUNOMODULATION,
AND AIDS
Proceedings of the 5th Annual Symposium,
N ashville, Tennessee
EDITORS
Herman Friedman, Un!versity of South Florida, Tampa, FL
John J. Madden, Emory University, Atlanta, GA
Thomas W. Klein, University of South Florida, Tampa, FL
EDITORIAL BOARD
Barbara Bayer, Georgetown University, Washington, D.C.
Jean Bidlack, University of Rochester, Rochester, NY
Sulie Chang, Seton Hall University, South Orange, NJ
Robert Donahoe, Emory University, Atlanta, GA
Toby K. Eisenstein, Temple University, Philadelphia, PA
Steven R. Specter, University of South Florida, Tampa, FL
EDITORIAL COORDINATOR AND MANAGING EDITOR
Ilona Friedman, University of South Florida, Tampa, FL
ix
CONTENTS
I. Cellular Mechanisms Involved in the Modulation of the Immune System by
Drugs of Abuse .............................................. .
Sulie L. Chang, Burt M. Sharp, and John J. Madden
2. Immunomodulation of Macrophage Functions by Opioids . . .. . .. . . . . .. . . . . 13
Ricardo Gomez-Flores and Richard J. Weber
3. Morphine Accelerates the Progression of Sepsis in an Experimental
Sepsis Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
Sabita Roy, Kelly J. Cain, Richard G. Charboneau, and Roderick A. Barke
4. Morphine Depresses Macrophage Numbers and Function in Mouse Spleens 33
T. K. Eisenstein, T. 1. Rogers, 1. 1. Meissler, Jr., M. W. Adler, and
M. E. Hilburger
5. Centrally-Mediated Opioid-Induced Immunosuppression: Elucidation of
Sympathetic Nervous System Involvement ........................ 43
William 1. Brinkman, David M. Hall, Jin-Liang Suo, and Richard J. Weber
6. The Expression of Interleukin-I f3 Converting Enzyme (ICE) in Rat Is
Decreased following Chronic Exposure to Morphine ................ 51
Gao-de Wu, Jennifer A. Graf, James E. Zadina, and Sulie L. Chang
7. Opioid Receptor Gene Expression in the Porcine Immune System .......... 59
Mary S. Pampusch, Mark A. Osinski, Janet R. Serie, Michael P. Murtaugh,
and David R. Brown
8. The Effects ofInteraction between Morphine and Interleukin-I on the
Immune Response ............................................ 67
Sulie L. Chang, Gao-de Wu, Nilesh A. Patel, Erich L. Vidal, and
Milan Fiala
9. Morphine Alters the Immune Response to Influenza Virus Infection in
Lewis Rats .................................................. 73
Mary E. Coussons-Read, Mary Daniels, and Matthew Ian Gilmour
xi
xii Contents
lO. Orphan Opioid Receptor Oligonucleotides Inhibit HIV-l Expression in
Human Brain Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
Chun C. Chao, Genya Gekker, Wen S. Sheng, Shuxian Hu, Horace H. Loh,
and Phillip K. Peterson
11. Opiate Effects on in Vitro Human Retroviral Infection . . . . . . . . . . . . . . . . . . . . 91
Susan Bell Nyland, Steven Specter, Jeong 1m-Sin, and Kenneth E. Ugen
12. FIV: A Lentivirus Model for Opiate Effects on Disease 101
Jean-Noel Billaud and Tom R. Phillips
13. Changes in Kappa Opioid Receptor Expression during Maturation of
Mouse Lymphocytes .......................................... 117
Tracey A. Ignatowski and Jean M. Bidlack
14. Modulation ofDPK Cell Function by the Kappa Opioid Agonist U50,488H 125
Liming Guan, Toby K. Eisenstein, Martin W. Adler, and Thomas J. Rogers
15. Properties of 1-13 Opiate Alkaloid Receptors in Macrophages, Astrocytes,
and HL-60 Human Promyelocytic Leukemia Cells .................. 137
M. H. Makman, K. Dobrenis, and C. K. Surratt
16. Morphine during Pregnancy in the Rat: Studies of Cellular Immunity in
Cross-Fostered Offspring. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149
James T. Martin, Sandra L. Nehlsen-Cannarella, Gary M. Gugelchuk,
and Omar R. Fagoaga
17. Western Blot Analysis of the Delta (0 )-Opioid Receptor in Activated
Murine T Cells ............................................... 159
Bonnie C. Miller
18. Morphine's Immunologic and Analgesic Effects: Comparison of
Time Course ................................................. 169
Christina J. Nelson, Linda A. Dykstra, and Donald T. Lysle
19. Immunomodulaticin Mediated by Microinjection of Morphine into the
Periaqueductal Gray Matter of the Mesencephalon. . . . . . . . . . . . . . . . . . 177
Jin-Liang Suo and Richard J. Weber
20. Novel Non-Peptidic Opioid Compounds with Immunopotentiating Effects 183
Mary E. Riley, Subramaniam Ananthan, and Richard J. Weber
21. Cocaine-Induced Release of Corticosterone Mediates Differential Effects on
T-Helperl and T-Helper2 Cell Responses. . . . . . . . . . . . . . . . . . . . . . . . . . 189
Denton F. Kump, Eric D. Stanulis, Michael P. Holsapple,
Daniel H. Conrad, and John A. Rosecrans
22. Cocaine Enhances Monocyte Migration across the Blood-Brain Barrier:
Cocaine's Connection to AIDS Dementia and Vasculitis? ............ 199
M. Fiala, X.-H. Gan, L. Zhang, S. D. House, T. Newton, M. C. Graves,
P. Shapshak, M. Stins, K.-S. Kim, M. Witte, and S. L. Chang