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.