DOSE-RESPONSE TO ETHANOL-CONTAINING LIQUID DIETS FOR USE IN A MURINE MODEL FOR STUDIES OF BIOLOGICAL EFFECTS DUE TO ETHANOL-CONSUMPTION

Dose-response experiments were performed to establish an optimum conce ntration of ethanol (EtOH) in liquid diet formulations for use with a murine model (C57BI/6) of potential biological effects attributable to EtOH consumption. An optimum concentration was predetermined to be th e highest EtOH concentration consumed by mice without resulting in a l oss of body weight. Feeding trials were performed using EtOH concentra tions that ranged from 25 to 36% ethanol-derived calories (EDC) during 7-day experiments, or 10 to 30% EDC fed during 21-day experiments. Th e parameters studied included body weight changes, diet consumptions, daily g EtOH kg(-1) body weight, as well as differences in mononuclear cell numbers from the spleen, thymus, and bone marrow. Diet consumpti ons by the EtOH groups and pair-fed (PF) groups were monitored by weig ht rather than by volume. During either 7-day or 21-day trials, diet c onsumptions were lower by groups receiving diets of higher EtOH concen trations; however, daily EtOH intake was maximal by groups fed diets o f 25% EDC in all experiments. These mice also gained weight, whereas m ice maintained on 30% EDC did not gain weight, and mice maintained on diets of 33 or 36% EDC lost significant body weight. Body weight chang es in PF groups were similar to their respective EtOH group. Changes i n mononuclear cell numbers of the spleen and thymus paralleled the cha nges seen in body weights. In the 7-day trials, cell counts declined p rogressively in groups maintained on diets of high EDC (greater than o r equal to 30% EDC) or their PF controls. From the 21-day trials, cell counts of both the 30% EDC group and their PF controls declined, comp ared with all other groups. Together, the conclusion drawn from these findings was that nutritional stress was principally responsible for t he mononuclear cell depletions. This contradicts previous reports and highlights the need for strict attention to the pair-feeding paradigm to avoid masking a nutritional component of such studies through overf eeding of the PF controls. Liquid diets of 25% EDC were determined to be optimal for immunological studies using a murine model, because thi s concentration maximizes EtOH consumption and maintains body weight o f the experimental animals.