STIMULATION OF TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION BY MYCOPLASMAS AND INHIBITION BY DEXAMETHASONE IN CULTURED ASTROCYTES

Elevated levels of tumor necrosis factor-alpha (TNFalpha) and other cytokines and eicosanoids in the central nervous system (CNS) have been noted in several human neurologic diseases, including multiple sclerosis and AIDS dementia. Recently it was shown that glial cells, especially astrocytes, are a major source of cytokines and eicosanoids. In the present study we have shown that astrocytes derived from fetal rat brain triggered by mycoplasmas produce TNFalpha and prostaglandin E2 (PGE2). Addition of mycoplasma (Mycoplasma capricolum isoalted from sheep and M. fermentans KL-4 from human) at a concentration of 1-50 mug protein/ml (2 x 10(7)-10(9) colony forming units/ml), as well as lipopolysaccharide (5 mug/ml), led to a 200-500-fold increase in TNFalpha and a 2.5-4.5-fold increase in PGE2 production. Preincubation of the cells with the synthetic glucocorticoid, dexamethasone (2 x 10(-5) -2 x 10(-8) M), as well as with the natural hormone, corticosterone, markedly inhibited the secretion of both TNFalpha and PGE2. Thus, mycoplasmas can be added to the wide variety of agents that stimulate glial cells to produce cytokines and eicosanoids, and may contribute to various CNS pathological manifestations. In addition, the ability of glucocorticoids to inhibit particularly the stimulated productions of TNFalpha and PGE2 may explain at least in part the therapeutic benefit of these agents in CNS inflammation and demyelination.