Mycoplasma triggering of nitric oxide production by central nervous system glial cells and its inhibition by glucocorticoids

Abstract

The same cytokines that have been implicated in the pathology of central nervous system (CNS) inflammatory diseases and demyelinating disease are also associated with the induction of nitric oxide (NO) production by macrophages and other somatic cells. Recently we have showed that mycoplasma can trigger the production of tumor necrosis factor (TNF)α and eicosanoids in rat astrocytes. In the present study, the effect of mycoplasma on NO production in rat glial cells was assessed. The addition of 10 μg/ml of membranes derived from M. capricolum (sheep isolate), M. fermentans (human isolate), or lipopolysaccharide (LPS) led to a 15- to 20-fold increase in NO production. The glucocorticoids dexamethasone and corticosterone, but not progesterone, markedly inhibited NO production. The addition of glucocorticoid prior or conjointly with the activator prevented large amounts of NO from being formed. Even when glucocorticoids were added 5 or 24 h after activation, effective inhibition of NO production was obtained. Thus, it is likely that glucocorticoids exert some of their ameliorating effects in neurological diseases by reducing the production of NO, cytokines and prostaglandins in the CNS.