Mycoplasma fermentans-induced inflammatory response of astrocytes:: Selective modulation by aminoguanidine, thalidomide, pentoxifylline and IL-10

Exposure of primary rat glial cells, mostly astrocytes, to heat-inactivated Mycoplasma fermentans triggers the production of tumor necrosis factor alpha (TNF alpha) nitric oxide (NO) and prostaglandin E-2 (PGE(2)). To attenuate the production of these proinflammatory mediators, four agents: aminoguanidine, pentoxifylline, thalidomide and IL-10 were added to astrocyte cultures. Aminoguanidine (1 and 3 mM), an inhibitor of inducible nitric oxide synthase (iNOS), suppressed the production of the three mediators. TNF alpha was the most sensitive to thalidomide, showing dose-response inhibition at concentrations of 20 mu g/ml, 50 mu g/ml and 250 mu g/ml. PGE(2) was affected only by concentrations of 50 mu g/ml and 250 mu g/ml, whereas NO responded solely to the highest amount of this inhibitor. The cytokine IL-10, at 10 U and 50 U, inhibited only TNF alpha production. Our results imply that selective suppression of proinflammatory mediators by various agents may prove feasible for amelioration of central nervous system inflammatory diseases.