Beta-endorphin modulation of lymphocyte proliferation: effects of ethanol.
BACKGROUND
We have previously shown that alcohol suppresses the natural killer (NK) cell activity of splenic lymphocytes partly by reducing the secretion of opioid peptide beta-endorphin (beta-EP) and its positive influence on NK-cell cytolytic activity in rats. The inhibition of NK-cell cytolytic activity was also associated with a reduced number of NK cells after chronic ethanol administration. Hence, the possibility arises that chronic ethanol may alter NK cell proliferation, survival, or both. In this study, we investigated whether ethanol treatment for 1 to 4 weeks reduces the proliferation of other lymphocyte subsets and whether beta-EP regulates ethanol's effect on lymphocyte proliferation.


METHODS
Male rats were ad libitum-fed rat chow, pair-fed with isocaloric liquid diet, or fed with ethanol-containing liquid diet for 1, 2, 3, or 4 weeks. Groups of these rats were infused with beta-EP with or without the delta-receptor antagonist naltrindol into the paraventricular nucleus of the hypothalamus. Splenocytes were isolated and used for flow cytometric analysis of the changes in the number of various lymphocyte subsets. Lymphocyte proliferation was determined by mitogen stimulation assays.


RESULTS
Ethanol consumption resulted in a reduction of the number of CD161+ NK cells, CD3+ T lymphocytes, CD4+ T-helper cells, and CD8a+ cytotoxic T cells in a time-dependent fashion. Alcohol consumption also suppressed the proliferative response of lymphocyte subsets to concanavalin A, phytohemagglutinin, and lipopolysaccharide. Beta-EP promoted the lymphocytes' proliferative response to mitogens, whereas naltrindol blocked the effects of the opioid. Chronic alcohol consumption reduced the proliferative response of lymphocytes to beta-EP.


CONCLUSIONS
These results suggest that chronic alcohol administration reduces immune function partly by decreasing the opioid-regulated mitogen-stimulated proliferation of lymphocyte subsets.
Boyadjieva
Nadka I
NI
Endocrinology Program, Center of Alcohol Studies, Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick 08901-8525, USA.
Dokur
Madhavi
M
Advis
Juan P
JP
Meadows
Gary G
GG
Sarkar
Dipak K
DK
D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005434:Flow Cytometry; D008070:Lipopolysaccharides / Q000494:pharmacology; D016131:Lymphocyte Subsets / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D001615:beta-Endorphin / Q000494:pharmacology*
D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D003208:Concanavalin A; D000431:Ethanol; D001615:beta-Endorphin