title: Morphine produces immunosuppressive effects in nonhuman primates at the proteomic and cellular levels.
abstract: 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.affiliation: Biological Sciences Division, Pacific Northwest National Laboratories, Richland, Washington 99352, USA.
authors.forename: Joseph N
authors.initials: JN
authors.lastname: Brown
authors.forename: Gabriel M
authors.initials: GM
authors.lastname: Ortiz
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Angel
authors.forename: Jon M
authors.initials: JM
authors.lastname: Jacobs
authors.forename: Marina
authors.initials: M
authors.lastname: Gritsenko
authors.forename: Eric Y
authors.initials: EY
authors.lastname: Chan
authors.forename: David E
authors.initials: DE
authors.lastname: Purdy
authors.forename: Robert D
authors.initials: RD
authors.lastname: Murnane
authors.forename: Kay
authors.initials: K
authors.lastname: Larsen
authors.forename: Robert E
authors.initials: RE
authors.lastname: Palermo
authors.forename: Anil K
authors.initials: AK
authors.lastname: Shukla
authors.forename: Theresa R
authors.initials: TR
authors.lastname: Clauss
authors.forename: Michael G
authors.initials: MG
authors.lastname: Katze
authors.forename: Joseph M
authors.initials: JM
authors.lastname: McCune
authors.forename: Richard D
authors.initials: RD
authors.lastname: Smith
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops; D003106:Colon / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D004734:Energy Metabolism / Q000187:drug effects; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D019394:Ki-67 Antigen; D007694:Killer Cells, Natural / Q000187:drug effects; D008198:Lymph Nodes / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D018655:Lymphocyte Count; D008254:Macaca nemestrina; D009020:Morphine / Q000097:blood / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects; D020543:Proteome / Q000032:analysis; D040901:Proteomics; D015398:Signal Transduction / Q000187:drug effects; D019966:Substance-Related Disorders; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D016207:Cytokines; D007166:Immunosuppressive Agents; D019394:Ki-67 Antigen; D020543:Proteome; D009020:Morphine