Decreasing endogenous glucocorticoids alters the ability of bone marrow cells to produce nitric oxide in response to stimulating agents

Glucocorticoids (GC) are essential for the body to maintain homeostasis. Patients with adrenal insufficiencies suffer from numerous health related problems including increased mortality due to sepsis. Here, we examine bone marrow (BM) cells from mice with adrenal insufficiency for their ability to produce nitric oxide (NO). Mice were injected with metyrapone (MR), an agent that selectively blocks glucocorticoid synthesis. BM cells were removed and tested for NO production. The stimulating agents LPS, TNF-α, IL-1β, and IL-4 were all able to synergize with IFN-γ, stimulating large concentrations of NO compared to normal mice. An important finding is that BM from injected mice produces NO in response to LPS alone, while normal BM cells do not. Experiments with anti IFN-γ antibody demonstrate that, in MR injected mice, LPS alone stimulated sufficient quantities of IFN-γ necessary for NO production. Our results demonstrate that reducing GCs alters regulation of NO production by BM cells at several levels.