Mechanism of ethanol-mediated immunosuppression in mice: ethanol suppresses T-cell proliferation without affecting IL2 production and IL2 receptor expression.
The effect of extended ethanol consumption in young C57BL/6 mice on T-cell proliferation was studied. Splenic cells of young mice (3-4 months old), fed with one of three different liquid diets (5% ethanol, maltose-substitute, or standard liquid diet) for 28-38 days were cultured with plant lectins to assess T-cell proliferation and IL2 production. Expression of T-cell subset markers (CD4+/CD8+) was also determined. Then, Con A-activated T blast cells were assessed for their ability to express IL2 receptor (IL2R) and to respond to IL2. Finally, the proliferative response of splenic cells to PMA/ionomycin was assessed. The results showed that both lectin- and PMA/ionomycin-induced mitogenesis and IL2-dependent proliferation of T-cells from ethanol diet-fed mice were diminished as compared with that of maltose-substitute diet or standard liquid diet. However, the ability of T-cells from ethanol diet-fed mice to produce IL2 and to express IL2 R or CD4+/CD8+ subset markers was not affected. Furthermore, the magnitude of ethanol-mediated suppression of T-cell proliferation induced by PMA/ionomycin was comparable with that induced by Con A. These results taken together indicate that ethanol suppresses T-cell proliferation by interfering with events following the IL2-IL2R interaction. Therefore, it is likely that ethanol inhibits murine T-cell proliferation by selectively affecting the progression (IL2R-mediated events) rather than the initiation (mitogenic receptor-mediated events) of the cell cycle.
Chang
M P
MP
Geriatric Research, Education and Clinical Center (GRECC), VA Medical Center West Los Angeles, CA.
Norman
D C
DC
D000818:Animals; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005434:Flow Cytometry; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000032:analysis / Q000096:biosynthesis*; D015759:Ionomycin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008320:Maltose / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D015375:Receptors, Interleukin-2 / Q000032:analysis*; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D000431:Ethanol; D015759:Ionomycin; D008320:Maltose