Yeh M, Chang M P, Norman D C
Harvard Medical School, Boston, MA 02115, USA.
Int J Immunopharmacol. 1996 Mar;18(3):219-26. doi: 10.1016/0192-0561(96)82091-1.
Although attempts have been made to assess the effect of ethanol on murine thymocyte proliferation, the mechanism which accounts for the immunosuppressive effect of ethanol on the thymocyte proliferation has not been elucidated. Thus, a mouse model was used to determine (1) whether there is a similarity in the effect of ethanol exposure in vitro and in vivo on the proliferative response of thymocytes to phytohemagglutinin (PHA), (2) whether ethanol exposure affects the responsiveness of thymocytes to exogenous interleukin (IL)-1 and IL-2, and (3) whether ethanol affects IL-1 production by peritoneal macrophages. We found that the proliferative response of thymocytes from mice fed on an ethanol-containing diet was significantly inhibited (P < 0.05) compared to that in mice fed on maltose or standard diets. We also observed that low concentrations of ethanol (12.5 mM) appeared to enhance the mitogenic response of thymocytes to PHA, but the response was not significantly greater than that of controls (P > 0.05). Ethanol at higher concentrations (25-100 mM) significantly suppressed the mitogenic response of thymocytes to PHA (P < 0.05) in a dose-dependent manner. Our data also revealed that (1) ethanol did not significantly suppress IL-1 secretion by adherent macrophages stimulated by LPS, and (2) the addition of exogenous IL-1 was insufficient to restore full responsiveness in thymocytes from ethanol-fed mice. Taken together, these results suggest that the suppressive effect of ethanol on thymocyte proliferation is not mediated by insufficient IL-1. Finally, we present novel evidence that addition of exogenous IL-2 completely restores the impaired proliferative response of thymocytes from ethanol-fed mice to control levels. In summary, our results demonstrate that ethanol inhibits thymocyte proliferation in response to PHA, and that the inhibition is not due to insufficient IL-1. We also report that addition of exogenous IL-2 is sufficient to restore full proliferative capacity to thymocytes from ethanol-fed mice.
尽管已经有人尝试评估乙醇对小鼠胸腺细胞增殖的影响，但乙醇对胸腺细胞增殖产生免疫抑制作用的机制尚未阐明。因此，我们使用了一个小鼠模型来确定：（1）体外和体内乙醇暴露对胸腺细胞对植物血凝素（PHA）增殖反应的影响是否相似；（2）乙醇暴露是否会影响胸腺细胞对外源白细胞介素（IL）-1和IL-2的反应性；（3）乙醇是否会影响腹膜巨噬细胞产生IL-1。我们发现，与喂食麦芽糖或标准饮食的小鼠相比，喂食含乙醇饮食的小鼠的胸腺细胞增殖反应受到显著抑制（P < 0.05）。我们还观察到，低浓度乙醇（12.5 mM）似乎增强了胸腺细胞对PHA的促有丝分裂反应，但该反应并不显著大于对照组（P > 0.05）。较高浓度（25 - 100 mM）的乙醇以剂量依赖的方式显著抑制了胸腺细胞对PHA的促有丝分裂反应（P < 0.05）。我们的数据还显示：（1）乙醇不会显著抑制脂多糖刺激的贴壁巨噬细胞分泌IL-1；（2）添加外源IL-1不足以恢复喂食乙醇小鼠的胸腺细胞的完全反应性。综上所述，这些结果表明乙醇对胸腺细胞增殖的抑制作用不是由IL-1不足介导的。最后，我们提供了新的证据，即添加外源IL-2可将喂食乙醇小鼠的胸腺细胞受损的增殖反应完全恢复到对照水平。总之，我们的结果表明乙醇抑制胸腺细胞对PHA的增殖反应，且这种抑制并非由于IL-1不足。我们还报告说，添加外源IL-2足以恢复喂食乙醇小鼠胸腺细胞的完全增殖能力。
