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. Molecular & Cellular

Role of Autophagy in HIV Pathogenesis and Drug Abuse

“…Firstly, certain DOA are associated with immunosuppressive effect, rendering drug users more prone to virus infection. Studies have found that morphine suppressed T cell activation in the lymph node, paralleled with a decrease in activation levels of T cells in peripheral blood in nonhuman primates [126]. Methamphetamine has been shown to accelerate the premature demise of activated T cells [127], and reduce the number of dendritic cells and natural killer cells [128,129].…”

Mitotic protein kinase CDK1 phosphorylation of mRNA translation regulator 4E-BP1 Ser83 may contribute to cell transformation

“…HeLa cells were disrupted, and proteins were tryptically digested, phosphopeptide enriched, TMT10 labeled, and high mass accuracy LC-MS/MS analyzed as previously described (47). Variations include use of TMT10 instead of iTRAQ labeling, cell lysate vs. tissue disruption, and use of Q Exactive Orbitrap MS. HEK293 cell LC-MS/MS analyses were performed identically, except for quantitation that used label-free approaches as previously described (48).…”

Effects of flurbiprofen axetil on postoperative serum IL-2 and IL-6 levels in patients with colorectal cancer

“…Currently, morphine is widely used for clinical analgesic therapy and has very important medical value. However, morphine has immunosuppressive properties and affects the immune system, including T lymphocytes, B lymphocytes, natural killer cells, macrophages, and mononuclear phagocytes (Brown et al, 2012;Abellan et al, 2014). Pain generally leads to immune suppression, which is attenuated by morphine; however, but morphine also has immunosuppressive properties that should not be ignored.…”