The immunosuppressive effects of chronic morphine treatment are partially dependent on corticosterone and mediated by the μ-opioid receptor

Jinghua Wang, Richard Charboneau, Sudha Balasubramanian, Roderick A. Barke, Horace H. Loh, Sabita Roy

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77 Scopus citations


Wild-type and μ-opioid receptor knock-out (MORKO) mice were used to investigate the role of corticosterone (CORT) and the μ-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 thymiclymphocyte 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-γ synthesis and splenic- and lymph node-lymphocyte proliferation and activation of macrophage TNF-α and IL-1β 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-γ synthesis and activation of macrophage-cytokine synthesis is CORT-independent and only partially dependent on sympathetic activation.

Original languageEnglish (US)
Pages (from-to)782-790
Number of pages9
JournalJournal of Leukocyte Biology
Issue number5
StatePublished - May 1 2002



  • Glucocorticoids
  • Hypothalamic pituitary adrenal axis
  • Neuroimmunomodulation
  • Sympathetic nervous system

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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