Morphine-induced thymic hypoplasia is glucocorticoid-dependent.
Mice administered morphine as a s.c. pellet implant exhibit a marked and sustained thymic hypoplasia as well as suppression of T lymphocyte functions. In the present study, the effects of morphine on thymocyte differentiation were characterized. Morphine produced a significant decrease in both the number and proportion of CD4+/CD8+ double positive (DP) cells. The percentage of the CD4+/CD8-, CD4-/CD8+, and CD4-/CD8- double negative subsets in these mice was proportionally increased. Morphine also increased the proportion of cells expressing either the epsilon-chain of the CD3 complex or the IL-2R. The initial reduction in the proportion of DP thymocytes appeared fully recovered by 10 days post-implantation, although the number of DP thymocytes gradually returned to normal over a 3-wk period. Morphine administration resulted in a marked increase in serum corticosterone levels, and a single injection of dexamethasone mimicked the effects of morphine on thymus differentiation. Furthermore, adrenalectomy abolished the morphine-induced decrease in CD4+/CD8+ thymocytes relative to a sham-operated group. The present findings are consistent with the hypothesis that morphine-induced thymic hypoplasia may be mediated by an increase in the circulating levels of corticosterone.
Sei
Y
Y
Laboratory of Neuroscience, NIDDK, National Institutes of Health, Bethesda, MD 20892.
Yoshimoto
K
K
McIntyre
T
T
Skolnick
P
P
Arora
P K
PK
D000315:Adrenalectomy; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D017252:CD3 Complex; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000166:cytology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D005938:Glucocorticoids; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D009271:Naltrexone; D009020:Morphine; D003907:Dexamethasone