Administration of glucocorticoids markedly increases the numbers of granulocytes and extrathymic T cells in the bone marrow

Glucocorticoids, steroid hormones, are widely used as an anti-inflammatory drug. However, clinicians have sometimes encountered adverse drug reactions such as ulcers and tissue damage. In this study, we investigated how such adverse reactions of glucocorticoids are evoked, using an experimental mice model. When hydrocortisone (0.5 or 1.0 mg/day/mouse) was administered dail y for 2 weeks, severe leukocytopenia was induced in all immune system organ s. However, granulocytes (Gr-1(+)Mac-1(+)) were increased in number in the bone marrow and peripheral blood. This seemed to be due to an elevated leve l of myelopoiesis in the bone marrow. As well as increasing in number, gran ulocytes were functionally activated as estimated by the Ca2+ influx and su peroxide production. The proportion of primordial T cells (CD3(int)IL-2R be ta(+)) in the thymus and the number of primordial T cells in the bone marro w also increased. Mice administered hydrocortisone became susceptible to st ress. Thus, these mice showed gastric ulcers when they were exposed to rest raint stress for 12 h. These results suggest that activated granulocytes an d primordial T cells might provide a mechanism involved in steroid ulcers a nd tissue damage, possibly through the superoxide production of granulocyte s and the autoreactivity of primordial T cells. (C) 1999 Academic Press.