Modulation of Hypothalamic beta-Endorphin-Regulated Expression of Natural Killer Cell Cytolytic Activity Regulatory Factors by Ethanol in Male Fischer-344 Rats.

摘要

BACKGROUND:: We have previously shown that ethanol administration suppresses natural killer (NK) cell cytolytic activity, partly by decreasing the action of hypothalamic beta-endorphin (beta-EP) on the spleens of male Fischer-344 rats. This study was conducted to examine the effects of ethanol and central administration of beta-EP on perforin, granzyme B, and the cytokine interferon (IFN)-gamma-factors that modulate NK cell cytolytic activity-to understand the mechanism involved in ethanol's suppression of NK cell activity. METHODS:: A group of male Fischer-344 rats were fed an ethanol-containing diet (8.7% v/v), and a control group was pair-fed an isocaloric diet. At the end of 2 weeks, both groups were infused with beta-EP 100 ng/hr into the paraventricular nucleus of the hypothalamus for 18 hr, and spleen tissues were immediately removed for analysis of perforin, granzyme B, and IFN-gamma messenger RNA (mRNA) and protein levels. The mRNA levels of perforin, granzyme B, and IFN-gamma were evaluated by quantitative real-time polymerase chain reaction, and the protein levels of perforin and granzyme B were analyzed by Western blot. RESULTS:: Paraventricular nucleus administration of beta-EP increased the mRNA and protein expression of granzyme B and mRNA expression of IFN-gamma in pair-fed animals. Ethanol significantly reduced both basal and beta-EP-induced levels of granzyme B and IFN-gamma. CONCLUSIONS:: These data suggest that chronic ethanol consumption suppresses beta-EP-induced NK cytolytic activity, granzyme B, and IFN-gamma in male Fischer-344 rats.