Immunotoxicity of alcohol in young and old mice. I. In vitro suppressive effects of ethanol on the activities of T and B immune cells of aging mice.
A murine aging model was employed to assess effects of ethanol exposure on the T-cell proliferative response to mitogenic stimulation and on the T cell-dependent primary antibody response to sheep red blood cells (RBC) in vitro. Splenic cells from young (3-5 months) and old (28-32 months) BALB/c mice were first assessed for their ability to produce interleukin (IL) 2 and proliferate in response to mitogenic stimulation in the presence of various doses of ethanol. Then, splenic T blast cells from young and old mice, generated by Con A-activation, were assessed for their IL2-dependent proliferative capacity in the presence of various doses of ethanol. Finally, splenic cells of young and old mice were assessed for their ability to generate plaque-forming cells (PFC) in response to sheep RBC in the presence of various doses of ethanol. The results revealed that ethanol has a much greater suppressive effect on old than young splenic T cells (10-15 times), as judged by their ability to proliferate in response to mitogenic stimulation. However, the magnitude of the difference in the suppressive effect is less when the cells are cycling (2 times). Furthermore, ethanol had only a minimal suppressive effect on IL2 production by T cells of both young and old mice, even at the concentration of 100 mM. These findings would suggest that the ethanol-mediated suppression of T cell proliferation of both young and old mice is more likely due to an impairment of metabolic event(s) associated with or subsequent to the interaction of IL2 and IL2 receptor leading to cellular replication.(ABSTRACT TRUNCATED AT 250 WORDS)
Geriatric Research, Education and Clinical Center (GRECC), VA Medical Center West Los Angeles, California 90073.
M P
MP
Chang
D C
DC
Norman
T
T
Makinodan
D000375:Aging / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015375:Receptors, Interleukin-2 / Q000187:drug effects; D012397:Rosette Formation; D013601:T-Lymphocytes / Q000187:drug effects*
D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D000431:Ethanol