Opioid-Like Activity of Naltrexone on Natural Killer Cell Cytolytic Activity and Cytokine Production in Splenocytes: Effects of Alcohol

Abstract

Chronic alcohol consumption has been shown to decrease the activity of natural killer (NK) cell cytolytic function and the production of various cytokines from the spleen. We have recently shown that naltrexone, an opiate receptor antagonist, when administered for a period of 2 weeks suppresses micro-opiate receptor binding but increases partial differential-opiate receptor activity in rat splenocytes. However, the effects of long-term naltrexone treatment on alcohol-induced alteration of NK cell cytolytic activity and cytokines production in splenocytes have not been determined. Male rats were pair-fed an isocaloric liquid diet or fed an ethanol-containing liquid diet for a period of 3 weeks. These rats were additionally treated after a week with a subcutaneous implant of either a naltrexone pellet or placebo pellet for 2 weeks. Splenocytes were isolated and used for determination of various cytokines interleukin (IL)-2, IL-4, and IL-6, and interferon-gamma (IFN-gamma) using enzyme-linked immunosorbent assay (ELISA), and the basal and IL-2-, IL-12-, or IL-18-induced NK cytolytic activity was measured using a standard 4-h (51)Cr release assay against YAC-1 lymphoma target cells. Ethanol consumption resulted in a reduction of the production of IL-2, IL-4, and IL-6 as well as the basal and cytokine-activated NK cell cytolytic activity and IFN-gamma production in splenocytes. Naltrexone administration increased the production of IL-2, IL-4, and IL-6 and the basal and cytokine-activated NK cell cytolytic activity and IFN-gamma production in the splenocytes of pair-fed and alcohol-fed rats. These results indicated that naltrexone treatment increases NK cell cytolytic activity and cytokine production in the spleen in vivo. Furthermore, these results identify the potential of the use of naltrexone in the treatment of immune deficiency in alcoholic and non-alcoholic patients.