Morphine Produces Immunosuppressive Effects in Non-human Primates at the Proteomic and Cellular Levels

Journal Article · Fri May 11 04:00:00 EDT 2012 · Molecular & Cellular Proteomics. MCP

DOI:https://doi.org/10.1074/mcp.M111.016121· OSTI ID:1050784

Brown, Joseph N; Ortiz, Gabriel M; Angel, Thomas E; Jacobs, Jon M; Gritsenko, Marina A; Chan, Eric Y; Purdy, David E; Murnane, Robert D; Larsen, Kay; Palermo, Robert E; Shukla, Anil K; Clauss, Therese RW; Katze, Michael G; McCune, Joseph M; Smith, Richard D

Morphine has long been known to have immunosuppressive properties in vivo, but the molecular and immunologic changes induced by it are incompletely understood. As a prelude to understanding how these changes might interact with lentiviral infection in vivo, animals from two non-human primate (NHP) species [African green monkey (AGMs) and pigtailed macaque (PTs)] were provided morphine and studied using a systems biology approach. Biological specimens were obtained from multiple sources (e.g., lymph node, colon, cerebrospinal fluid (CSF), 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 inter-organ, inter-individual, and inter-species 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 cells counts. While 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 the lymph node, with decreased abundance of protein mediators involved in the functional categories of energy metabolism, signaling, and maintenance of cell structure. These findings have relevance for understanding the impact of heroin addiction and the opioids used to treat addiction as well as on the interplay between opioid abuse and the response to infection with agents such as the human immunodeficiency virus, type 1 (HIV).

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1050784
• Report Number(s): PNNL-SA-83778; 33700; 40072; 400412000
• Journal Information: Molecular & Cellular Proteomics. MCP, Journal Name: Molecular & Cellular Proteomics. MCP Journal Issue: 9 Vol. 11; ISSN 1535-9476
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ABUNDANCE
AIDS VIRUS
ANIMALS
BLOOD
BLOOD PLASMA
CEREBROSPINAL FLUID
DOSES
Environmental Molecular Sciences Laboratory
HEROIN
HUMAN POPULATIONS
IN VIVO
LARGE INTESTINE
LYMPH NODES
MACACUS
MATURATION
METABOLISM
MONKEYS
MORPHINE
NATURAL KILLER CELLS
NEUTROPHILS
PRIMATES
PROTEINS
immunosuppression
morphine
non-human primate
proteomics