Document Detail


Morphine produces immunosuppressive effects in nonhuman primates at the proteomic and cellular levels.
MedLine Citation:
PMID:  22580588     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Morphine has long been known to have immunosuppressive properties in vivo, but the molecular and immunologic changes induced by it are incompletely understood. To explore how these changes interact with lentiviral infections in vivo, animals from two nonhuman primate species (African green monkeys and pigtailed macaques) were provided morphine and studied using a systems biology approach. Biological specimens were obtained from multiple sources (e.g. lymph node, colon, cerebrospinal fluid, and peripheral blood) before and after the administration of morphine (titrated up to a maximum dose of 5 mg/kg over a period of 20 days). Cellular immune, plasma cytokine, and proteome changes were measured and morphine-induced changes in these parameters were assessed on an interorgan, interindividual, and interspecies basis. In both species, morphine was associated with decreased levels of Ki-67(+) T-cell activation but with only minimal changes in overall T-cell counts, neutrophil counts, and NK cell counts. Although changes in T-cell maturation were observed, these varied across the various tissue/fluid compartments studied. Proteomic analysis revealed a morphine-induced suppressive effect in lymph nodes, with decreased abundance of protein mediators involved in the functional categories of energy metabolism, signaling, and maintenance of cell structure. These findings have direct relevance for understanding the impact of heroin addiction and the opioids used to treat addiction as well as on the potential interplay between opioid abuse and the immunological response to an infective agent.
Authors:
Joseph N Brown; Gabriel M Ortiz; Thomas E Angel; Jon M Jacobs; Marina Gritsenko; Eric Y Chan; David E Purdy; Robert D Murnane; Kay Larsen; Robert E Palermo; Anil K Shukla; Theresa R Clauss; Michael G Katze; Joseph M McCune; Richard D Smith
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-05-11
Journal Detail:
Title:  Molecular & cellular proteomics : MCP     Volume:  11     ISSN:  1535-9484     ISO Abbreviation:  Mol. Cell Proteomics     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-03     Completed Date:  2013-02-26     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  101125647     Medline TA:  Mol Cell Proteomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  605-18     Citation Subset:  IM    
Affiliation:
Biological Sciences Division, Pacific Northwest National Laboratories, Richland, Washington 99352, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cercopithecus aethiops
Colon / drug effects
Cytokines / blood
Energy Metabolism / drug effects
Immune Tolerance*
Immunosuppressive Agents / pharmacology*
Ki-67 Antigen
Killer Cells, Natural / drug effects
Lymph Nodes / drug effects
Lymphocyte Activation / drug effects*
Lymphocyte Count
Macaca nemestrina
Morphine / blood,  cerebrospinal fluid,  pharmacology*
Neutrophils / drug effects
Proteome / analysis
Proteomics*
Signal Transduction / drug effects
Substance-Related Disorders
T-Lymphocytes / drug effects,  immunology
Grant Support
ID/Acronym/Agency:
P01 DA026134/DA/NIDA NIH HHS; P01 DA026134/DA/NIDA NIH HHS; P41 GM103493/GM/NIGMS NIH HHS; P41 RR018522/RR/NCRR NIH HHS; P51 RR000166/RR/NCRR NIH HHS; T32 AI007641/AI/NIAID NIH HHS; T32 AI060530/AI/NIAID NIH HHS; T32 AI07140/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 0/Immunosuppressive Agents; 0/Ki-67 Antigen; 0/Proteome; 57-27-2/Morphine
Comments/Corrections

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