Prednisolone inhibits LPS-induced bone marrow suppressor cell activity in vitro but not in vivo

Abstract

Glucocorticoids are used clinically to treat a variety of inflammatory diseases including endotoxemia. We hypothesized that injecting mice with the steroid prednisolone (pred) would mitigate the enhanced bone marrow (BM) natural suppressor (NS) cell activity that occurs in mice after receiving an injection of lipopolysaccharide (LPS). In vitro, prednisolone blocked the ability of NS cells to produce the immunosuppressive molecule nitric oxide (NO) and also the ability to suppress T cell proliferation. Prednisolone acted both indirectly, by blocking synthesis of cytokines necessary for NS cell activation, and also directly on NS cells, by blocking production of NO. In vivo, variable results were obtained. Prednisolone at 20 μg/gm did decrease NS activity when injected into normal mice. However, when mice were injected with both LPS and prednisolone (0.2 or 20 μg/gm), a large increase in BM NS activity was observed. The increase was evident in both the ability of the BM cells to suppress T cell proliferation and to produce NO. The data show that, in vivo, the steroid prednisolone in conjunction with the inflammatory compound LPS act to enhance BM NS activity.