title: The immunosuppressive effects of chronic morphine treatment are partially dependent on corticosterone and mediated by the mu-opioid receptor.
abstract: Wild-type and mu-opioid receptor knockout (MORKO) mice were used to investigate the role of corticosterone (CORT) and the mu-opioid receptor (MOR) in chronic morphine-mediated immunosuppression. We found that although plasma CORT concentrations in CORT infusion (10 mg/kg/day) and morphine-pellet implantation (75 mg) mice were similar (400-450 ng/ml), chronic morphine treatment resulted in a significantly higher (two- to threefold) inhibition of thymic, splenic, and lymph node cellularity; inhibition of thymic-lymphocyte proliferation; inhibition of IL-2 synthesis; and activation of macrophage nitric oxide (NO) production when compared with CORT infusion. In addition, results show that the inhibition of IFN-gamma synthesis and splenic- and lymph node-lymphocyte proliferation and activation of macrophage TNF-alpha and IL-1beta synthesis occurred only with chronic morphine treatment but not with CORT infusion. These morphine effects were abolished in MORKO mice. The role of the sympathetic nervous system on morphine-mediated effects was investigated by using the ganglionic blocker chlorisondamine. Our results show that chlorisondamine was able to only partially reverse morphine's inhibitory effects. The results clearly show that morphine-induced immunosuppression is mediated by the MOR and that although some functions are amplified in the presence of CORT or sympathetic activation, the inhibition of IFN-gamma synthesis and activation of macrophage-cytokine synthesis is CORT-independent and only partially dependent on sympathetic activation.
authors: Department of Pharmacology, University of Minnesota, Minneapolis, MN 55417, USA.
authors: Jinghua
authors: J
authors: Wang
authors: Richard
authors: R
authors: Charboneau
authors: Sudha
authors: S
authors: Balasubramanian
authors: Roderick A
authors: RA
authors: Barke
authors: Horace H
authors: HH
authors: Loh
authors: Sabita
authors: S
authors: Roy
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002714:Chlorisondamine / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology* / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D004343:Drug Implants; D005730:Ganglionic Blockers / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000502:physiology*
chemical_list: D016207:Cytokines; D004343:Drug Implants; D005730:Ganglionic Blockers; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D009569:Nitric Oxide; D009020:Morphine; D002714:Chlorisondamine; D003345:Corticosterone