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The influence of opioids on the humoral and cell-mediated immune responses in mice. The role of macrophages

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Abstract

Background

Our experiments were aimed to test the influence of treatment with different opioids (morphine, fentanyl, methadone) on the humoral and cell-mediated immune responses.

Methods

Mice were treated intraperitoneally (ip) with opioids for several days and next either immunized with sheep red blood cells (SRBC) to test the antibody production or skin-sensitized with hapten picryl chloride (PCL) to induce contact hypersensitivity (CHS). In addition, the effects of opioids on the production of reactive oxygen intermediates (ROIs) and cytokines by peritoneal macrophages (Mf) and on the expression of surface markers on these cells and blood leukocytes were estimated.

Results

Opioids caused an enhancement of ROIs and cytokines production when macrophages were stimulated with zymosan or lipopolysaccharide (LPS) and reduced the expression of antigen presentation markers on Mf. Numbers of anti-SRBC plaque forming cells (PFC) and antibodies titres were lower in mice treated with all tested opioids. Depending on the use of particular opioid and the phase of allergic reaction, effects of the treatment on CHS were diverse. While morphine decreased the early and late phases of induction of CHS responses, methadone increased both reactions. In case of the effector phase of CHS, morphine and fentanyl increased both its early and late stages, while methadone decreased the late reaction. Treatment of recipients with opioids had diverse influence on the passive transfer of CHS in these animals.

Conclusions

Our experiments show that the action of opioids on the immune system is a complex phenomenon dependent on such variables as type of opioid, character of response (humoral versus cellular) and types of cells involved. Here Mf seem to play a significant role.

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Abbreviations

APCs:

antigen presenting cells

CD:

cluster of differentiation

CHS:

contact hypersensitivity

DNFB:

1-fluoro-2,4-dinitrobenzene

DPBS:

Dulbecco’s phosphate buffered saline

FCS:

fetal calf serum, FcψR - Fcψ receptor

FITC:

fluorescein isothiocyanate

IL:

interleukin

LPS:

lipopolysaccharide

Mf:

macrophages

mAb:

monoclonal antibody

NK:

natural killer cells

NMDA:

N-methyl-D-aspartate

Oil-Mf:

oil-induced peritoneal macrophages

OPs:

opioids

OX:

oxazolone

PAMPs:

pathogen associated molecular patterns

PCL:

picryl chloride (1,3,5-trinitrophenyl chloride)

PE:

phycoerythrin

PFC:

plaque forming cells

R-Mf:

resident peritoneal macrophages

ROIs:

reactive oxygen intermediates

SRBC:

sheep red blood cells

TGF:

transforming growth factor

T-Mf:

thioglycollate-induced peritoneal macrophages

TNBSA:

trinitrobenzene sulfonic acid

TNF:

tumor necrosis factor

TNP:

2,4,6-trinitrophenyl

Treg:

T regulatory cells

vs.:

versus

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Correspondence to Krzysztof Bryniarski.

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Filipczak-Bryniarska, I., Nowak, B., Sikora, E. et al. The influence of opioids on the humoral and cell-mediated immune responses in mice. The role of macrophages. Pharmacol. Rep 64, 1200–1215 (2012). https://doi.org/10.1016/S1734-1140(12)70916-7

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  • DOI: https://doi.org/10.1016/S1734-1140(12)70916-7

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