Chronic ethanol inhibits NK cell cytolytic activity: role of opioid peptide beta-endorphin.
The role of beta-endorphin (beta-EP) in ethanol-altered NK cell cytolytic activity is studied using male Fischer-344 rats as an animal model. Ethanol was administered for 1, 2, 3, or 4 wk in a liquid diet containing 8.7% ethanol (v/v), which means that 37% of the total calories were derived from ethanol. Rats treated with ethanol for 1 wk showed an increase in hypothalamic and plasma levels of immunoreactive (IR)-beta-EP, but displayed no significant effect on NK cell activity determined by (51)Cr release assay, as compared with those in pair-fed and ad libitum-fed animals. However, animals treated with ethanol for 2, 3, or 4 wk showed decreased hypothalamic and plasma levels of IR-beta-EP and decreased splenic NK cell activity. No significant decrease in the number of splenocytes and NK cells or in the percentage of NK cells was seen until after 3 and 4 wk of ethanol treatment. Exposure in vitro of splenic lymphocytes obtained from control animals to various concentrations of beta-EP increased NK cell activity. The opiate antagonist naltrexone blocked the beta-EP-stimulated effect. The in vitro NK cell response to beta-EP was reduced in the splenocytes obtained from animals treated with ethanol for 2 wk, but not in those obtained from animals treated with ethanol for 1 wk as compared with those in control animals. Additionally, beta-EP administration into the paraventricular nucleus of the hypothalamus stimulated NK cell cytolytic activity, whereas the opiate blocker administration reduced NK cell activity. The NK cell responses to paraventricular nucleus beta-EP were reduced in the animals treated with ethanol for 2 wk. These data provide evidence for the first time that ethanol inhibits NK cell cytolytic activity, possibly by reducing beta-EP-regulated splenic NK cell function.
Boyadjieva
N
N
Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
Dokur
M
M
Advis
J P
JP
Meadows
G G
GG
Sarkar
D K
DK
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007031:Hypothalamus / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D018655:Lymphocyte Count; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D013154:Spleen / Q000276:immunology; D014407:Tumor Cells, Cultured; D001615:beta-Endorphin / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*
D000906:Antibodies; D009292:Narcotic Antagonists; D000431:Ethanol; D009271:Naltrexone; D001615:beta-Endorphin