No detrimental effect from chronic exposure to buprenorphine on corticosteroid-binding globulin and corticosensitive immune parameters.
Opioid drugs reportedly regulate the immune system via their effects on the hypothalamic- pituitary-adrenal (HPA) axis. The present study was carried out to assess the effects of chronic exposure to buprenorphine on HPA axis activation, corticosteroid-binding globulin (CBG), the main glucocorticoid (GC) carrier, and the immune system. Results show that buprenorphine, delivered by osmotic pump subcutaneously in C57BL/6 male mice during a 10-day period, caused a marked decrease in total corticosterone (CORT) levels at day 1 of exposure. CORT levels then increased with maximal values observed at day 5 of exposure. After day 5, total CORT levels gradually decreased and returned to control values. No significant changes were observed in CBG protein levels and mRNA expression in the liver. Since CBG levels remained unchanged, the percentage of free CORT values in buprenorphine mice did not differ from control values. Thus, the variations observed in the amount of free CORT were related only to changes measured in total CORT. These endocrine changes did not have a significant impact on the immune parameters measured. Total CD(4)+ and CD(8)+ splenic and thymic populations were not modulated by buprenorphine. However, splenocytes from mice exposed to buprenorphine after 5 days exhibited greater proliferation upon anti-TCR monoclonal antibody stimulation than saline-exposed mice. These results indicate that buprenorphine can be safely used because it did not have significant effects on GC availability for immune corticosensitive cells.
INRS-Institut Armand-Frappier, Pointe-Claire, H9R 1G6 Quebec, Canada.
M
M
D'Elia
J
J
Patenaude
C
C
Hamelin
D R
DR
Garrel
J
J
Bernier
D000701:Analgesics, Opioid / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002047:Buprenorphine / Q000009:adverse effects / Q000276:immunology* / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D003345:Corticosterone / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D000701:Analgesics, Opioid; D002352:Carrier Proteins; D002047:Buprenorphine; D012313:RNA; D003345:Corticosterone