POSSIBLE ROLES FOR GLUCOCORTICOIDS AND APOPTOSIS IN THE SUPPRESSION OF LYMPHOPOIESIS DURING ZINC-DEFICIENCY - A REVIEW

Thymic atrophy and lymphopenia are immunological hallmarks of many for ms of malnutrition including deficiencies in zinc. Extreme thymic atro phy (70-80%) along with a 50% loss of splenocytes in mice maintained o n a zinc deficient diet (ZD) for 30 days suggested that the deficiency might be altering lymphopoiesis or the production of new lymphocytes by the bone marrow. As shown herein, mice who were marginally zinc def icient being 72-75% the body weight of adequately fed controls, exhibi ted a 50% decline in pre B-cells and a 25% decline in immature B-cells . The mature B-cells of the marrow appeared fairly resistant to effect s of suboptimal zinc intake. Interesting, this pattern was similar to results obtained by treating bone marrow cells with levels of glucocor ticoids analogous to those found in nutritionally deficient rodents. F urthermore, these same concentrations of steroids were shown to induce significant levels of apoptosis or cell death among pre and immature B-cells which accounted for their declining numbers subsequent to expo sure to glucocorticoid. In order to better ascertain the potential rol e of glucocorticoids generated during zinc deficiency on lymphopoietic processes, adrenalectomies were performed in an attempt to remove glu cocorticoids from the equation. Subsequently, adrenalectomized and sha m operated mice were placed on a ZD or zinc adequate diet (ZA). Levels of steroids at the time of sacrifice were elevated six fold in non-ad renalectomized ZD mice compared to ZD adrenalectomized mice. Removal o f the adrenal gland protected the thymus of ZD mice from atrophy and a lso provided substantial protection of lymphopoietic processes. This s uggests that glucocorticoid mediated apoptosis may play a significant role in the loss of developing lymphoid cells by altering lymphopoiesi s in zinc deficient rodents.