Modulation of hypothalamic beta-endorphin-regulated expression of natural killer cell cytolytic activity regulatory factors by ethanol in male Fischer-344 rats.
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.
Endocrinology Program, Center of Alcohol Studies and Department of Animal Sciences, Rutgers, The State University of New Jersey, New Brunswick, New Jersey 08901-8525, USA.
Madhavi
M
Dokur
Nadka I
NI
Boyadjieva
Juan P
JP
Advis
Dipak K
DK
Sarkar
D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D001615:beta-Endorphin / Q000494:pharmacology*
D012333:RNA, Messenger; D000431:Ethanol; D001615:beta-Endorphin