TY - JOUR
T1 - The immunosuppressive effects of chronic morphine treatment are partially dependent on corticosterone and mediated by the μ-opioid receptor
AU - Wang, Jinghua
AU - Charboneau, Richard
AU - Balasubramanian, Sudha
AU - Barke, Roderick A.
AU - Loh, Horace H.
AU - Roy, Sabita
PY - 2002/5/1
Y1 - 2002/5/1
N2 - 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.
AB - 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.
KW - Glucocorticoids
KW - Hypothalamic pituitary adrenal axis
KW - Neuroimmunomodulation
KW - Sympathetic nervous system
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M3 - Article
C2 - 11994502
AN - SCOPUS:0036587745
VL - 71
SP - 782
EP - 790
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 5
ER -