DESCRIPTION: High alcohol intake has been shown to compromise cell-mediated and humoral immunity by altering the function of various lymphocytes, including the natural killer (NK) cells, which participate in the defense against infection, tumor development and metastasis. How alcohol alters NK cell function is not known. Preliminary studies using male rats as an animal model demonstrate that alcohol consumption can suppress splenic NK cytolytic activity and decrease hypothalamic and plasma B-endorphin levels. Furthermore, opioid peptide B-endorphin stimulates NK cell cytolytic activity in vitro. Since levels of endogenous B-endorphin are reduced following alcohol treatment, a question arises as to whether the abnormality in NK cell activity in alcohol-treated animals is secondary to altered endogenous opioid activity. The goal of this proposal is to examine the role of opioid peptide B-endorphin in ethanol-modulated NK cell function. Three specific aims are proposed: 1) to further characterize the effects of ethanol on central and peripheral B-EP by determining the effects on B-EP production and secretion in the hypothalamus and pituitary and ethanol's effects on NK cell cytolytic activity by using NK-enriched splenocytes and 51Cr release assays; 2) to identify the mediatory role of B-EP by determining the actions of B-EP and its antagonist naltrexone on ethanol-modulated NK cell activity, and 3) to determine the neurochemical mechanisms by studying the role of corticotropin-releasing hormone and norepinephrine in B-EP-regulated NK cell activity in alcohol-treated rats. These studies have the potential to elucidate important neuroendocrine mechanisms mediating ethanol-induced immune dysfunction and may indicate potential therapeutic uses of the opiate antagonist naltrexone, in controlling alcohol-induced immune dysfunction.
|Effective start/end date||7/10/99 → 3/31/04|
- National Institutes of Health: $153,649.00
- National Institutes of Health: $191,936.00
- National Institutes of Health: $163,006.00
- National Institutes of Health: $158,259.00