Journal article
Exogenous IL-15 in combination with IL-15R alpha rescues natural killer cells from apoptosis induced by chronic alcohol consumption
Alcoholism, clinical and experimental research, Vol.33(3), pp.419-427
03/2009
Handle:
https://hdl.handle.net/2376/105245
PMCID: PMC2651996
PMID: 19120059
Abstract
Chronic alcohol consumption reduces the percentage and number of peripheral natural killer (NK) cells in mice and in humans. The underlying mechanism for these changes is only partly known. We recently found that chronic alcohol consumption inhibits NK cell release from the bone marrow (BM) and that this is associated with a decrease in splenic NK cells. The number of peripheral NK cells is tightly controlled by homeostatic proliferation. It is not known whether this mechanism is initiated in response to the reduction in splenic NK cells, or if so, why the steady state levels of NK cells are not restored.
To examine this mechanism, female C57BL/6 mice were given 20% w/v alcohol in the drinking water for 3 months. NK cell proliferation and apoptosis were determined before and after treatment with IL-15 alone or combined with its alpha receptor.
Chronic alcohol consumption invoked homeostatic proliferation of splenic NK cells in an attempt to return NK cells to normal levels; however, this did not happen due to enhanced apoptosis of NK cells relative to proliferation. Chronic alcohol consumption decreased IL-15 producing cells in the spleen but not in the BM. The numbers of NK cells in the alcohol-consuming mice returned to normal levels in the spleen and were higher than normal in the BM after 2 daily injections of IL-15; however, the enhanced rate of apoptosis due to alcohol consumption was not decreased in the spleen or BM. Combined IL-15 and IL-15R alpha treatment decreased apoptosis of NK cells from alcohol-consuming mice to levels similar to untreated water-drinking mice and greatly increased the percentage and number of NK cells in both the spleen and BM.
Chronic alcohol consumption causes a self-unrecoverable loss of NK cells in the spleen by compromising NK cell release from the BM and enhancing splenic NK cell apoptosis that can be reversed with IL-15/IL-15R alpha treatment.
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Details
- Title
- Exogenous IL-15 in combination with IL-15R alpha rescues natural killer cells from apoptosis induced by chronic alcohol consumption
- Creators
- Hui Zhang - Cancer Prevention & Research Center, Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, Washington 99164-6713, USAGary G Meadows
- Publication Details
- Alcoholism, clinical and experimental research, Vol.33(3), pp.419-427
- Academic Unit
- Pharmaceutical Sciences, Department of
- Publisher
- England
- Grant note
- R21 AA014200 / NIAAA NIH HHS R21 AA014200-03 / NIAAA NIH HHS AA014200 / NIAAA NIH HHS R01 AA007293-18 / NIAAA NIH HHS AA07293 / NIAAA NIH HHS R01 AA007293 / NIAAA NIH HHS
- Identifiers
- 99900546836101842
- Language
- English
- Resource Type
- Journal article