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. Ethano l was administered for 1, 2, 3, or 4 wk in a liquid diet containing 8.7% et hanol (v/v), which means that 37% of the total calories were derived from e thanol. Rats treated with ethanol for 1 wk showed an increase in hypothalam ic and plasma levels of immunoreactive (IR)-beta -EP, but displayed no sign ificant effect on NK cell activity determined by Cr-51 release assay, as co mpared 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 pl asma levels of IR-beta -EP and decreased splenic NK cell activity. No signi ficant decrease in the number of splenocytes and NK cells or in the percent age of NK cells was seen until after 3 and 4 wk of ethanol treatment. Expos ure in vitro of splenic lymphocytes obtained from control animals to variou s concentrations of beta -EP increased NK cell activity. The opiate antagon ist 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 treat ed with ethanol for I wk as compared with those in control animals. Additio nally, beta -EP administration into the paraventricular nucleus of the hypo thalamus stimulated NK cell cytolytic activity, whereas the opiate blocker administration reduced NK cell activity. The NK cell responses to paraventr icular nucleus beta -EP were reduced in the animals treated with ethanol fo r 2 wk. These data provide evidence for the first time that ethanol inhibit s NK cell cytolytic activity, possibly by reducing beta -EP-regulated splen ic NK cell function.