Role of adrenal cortical activation in the immunosuppressive effects of chronic morphine treatment.
Implantation of a 75-mg morphine pellet in sham-adrenalectomized male C3H/HeN mice resulted in significant elevations of serum corticosterone levels within 6 h. Corticosterone levels remained elevated (3- to 4-fold) for 72 h and had returned to normal by 120 h postimplantation. Within 48 h of pellet implantation, morphine-pelleted mice exhibited marked reductions in spleen (35%) and thymus weight (56%) relative to values in placebo-pelleted controls. In addition, adrenal hypertrophy was observed in the morphine-pelleted shams (50% increase in adrenal weight relative to placebo. The magnitude of splenic and thymic atrophy was reduced by about 50% in adrenalectomized morphine-pelleted mice (17% and 22% reductions, respectively) compared to that in adrenalectomized mice implanted with placebo pellets. Lymphocyte proliferative responses to the T-cell mitogen Concanavalin-A and the B-cell mitogen bacterial lipopolysaccharide were also significantly reduced in the morphine-pelleted sham mice. Morphine-induced suppression of Concanavalin-A- or lipopolysaccharide-stimulated lymphocyte proliferation was absent in adrenalectomized mice. Effects similar to adrenalectomy (e.g. lessening of magnitude of morphine-induced suppression of lymphoid organ weight and lymphocyte proliferation) were found in morphine-pelleted mice given the glucocorticoid receptor antagonist RU-486 at a dose of 10 mg/kg, twice daily. These studies imply that morphine-induced immunosuppression is at least in part mediated by the increase in serum corticosterone levels after implantation of the morphine pellet.
Bryant
H U
HU
Department of Immunology, Pulmonary and Leukotriene Research, Eli Lilly Co., Indianapolis, Indiana 46285.
Bernton
E W
EW
Kenner
J R
JR
Holaday
J W
JW
D000302:Adrenal Cortex / Q000502:physiology*; D000315:Adrenalectomy; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D004343:Drug Implants; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D015735:Mifepristone / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000033:anatomy & histology / Q000166:cytology; D013950:Thymus Gland / Q000033:anatomy & histology; D013997:Time Factors
D004343:Drug Implants; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D003208:Concanavalin A; D015735:Mifepristone; D009020:Morphine; D003345:Corticosterone