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Effects of Opioid Tolerance and Withdrawal on the Immune System

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Abstract

Review of the robust literature using acute drug injection paradigms points clearly to the conclusion that morphine is immunosuppressive. In contrast, studies of the effect of subacute or chronic administration of morphine on immune function is limited, with variable results. In some cases tolerance to the immunosuppressive effects of the drug is clearly demonstrated, but in other cases, selected immune parameters do not demonstrate tolerance. Discrepancies in findings may result from differences in species or route and manner of drug administration. Even fewer studies (total of 10) have been published on the effects of withdrawal on immune function. Most immune parameters tested are suppressed following drug withdrawal. Recovery time to baseline response levels varies in the studies. In the single report of withdrawal in humans, immune function was suppressed for up to 3 years. It is clearly established that withdrawal suppresses capacity of murine spleen cells to make an ex vivo antibody response, which contrasts with evidence of polarization of the lymphocytes towards a Th2 phenotype. Several laboratories have shown that subacute and chronic exposure to morphine, as well as drug withdrawal, sensitize to the lethal effects of bacterial lipopolysaccharide. Underlying sepsis, combined with morphine-induced hypofunction of the hypothalamic-pituitaryadrenal (HPA) axis, may be occult variables modulating immune responses during opioid administration and withdrawal. As episodes of withdrawal are common among drug abusers, more intensive investigation is warranted on the effects of withdrawal on immune function, on mechanisms of immune modulation, and on sensitization to infection.

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Abbreviations

CD:

cluster of differentiation

CD3:

antigenic marker found on all T cells

Con A:

concanavailin A, a protein from the jack bean (Canavalia ensiformis) that stimulates T cells to divide

DTH:

delayed-type hypersensitivity

FIV:

feline immunodeficiency virus

fMLP:

a tripeptide composed of formyl-methionine, leucine, and phenylalanine, which is chemotactic and promotes inflammation

HPA:

hypothalamic–pituitary–adrenal axis

IFN-α:

interferon alpha

IFN-γ:

interferon gamma

IgM:

immunoglobulin of the IgM type

IL:

interleukin

IL-1:

interleukin 1

IL-2:

interleukin 2

IL-12:

interleukin 12

i.c.v.:

intracerebral vascular

i.p.:

intraperitoneal

LPS:

lipopolysaccharide, a component of the outer membrane of gram-negative bacteria that has endotoxic activity and can lead to a sepsis syndrome

Mitogen:

a substance that causes lymphocytes to divide without ligating their antigen receptors

NK:

natural killer (cells or activity)

s.c.:

subcutaneous

Th1 :

T helper type 1 cells

Th2 :

T helper type 2 cells

TNF-α:

tumor necrosis factor alpha, a cytokine that induces widespread inflammatory changes and symptoms of sepsis

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Acknowledgements

This study was supported by National Institute of Drug Abuse grants DA14223, DA11134, DA13429 and DA06650. The authors thank Dr. Martin W. Adler for a critical reading of the manuscript.

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Authors and Affiliations

  1. Center for Substance Abuse Research and Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, PA, 19140, USA

    Toby K. Eisenstein, Pu Feng, Nita K. Thingalaya & Joseph J. Meissler

  2. Center for Substance Abuse Research and Fels Institute of Cancer Research and Molecular Biology, Temple University School of Medicine, 3307 North Broad Street, Philadelphia, PA, 19140, USA

    Rahil T. Rahim

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  1. Toby K. Eisenstein
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  2. Rahil T. Rahim
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  3. Pu Feng
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Correspondence to Toby K. Eisenstein.

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Eisenstein, T.K., Rahim, R.T., Feng, P. et al. Effects of Opioid Tolerance and Withdrawal on the Immune System. Jrnl Neuroimmune Pharm 1, 237–249 (2006). https://doi.org/10.1007/s11481-006-9019-1

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  • DOI: https://doi.org/10.1007/s11481-006-9019-1

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