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Chronic ethanol inhibits NK cell cytolytic activity: role of opioid peptide beta-endorphin
N Boyadjieva1, M Dokur, J P Advis
1Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA.
Abstract:
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.
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