INHIBITION OF THE INDUCTION OF THE INDUCIBLE NITRIC-OXIDE SYNTHASE INMURINE BRAIN MICROGLIAL CELLS BY SODIUM-SALICYLATE

The induction of the inducible nitric oxide synthase (iNOS) has been p roposed to play a role in a variety of inflammatory diseases. Sodium s alicylate (NaSal) is the most commonly used antiinflammatory agent. We investigated whether NaSal can diminish the induction of iNOS in muri ne brain microglial cells. In primary cultures, interferon-gamma (IFN- gamma) or lipopolysaccharide (LPS) separately did not stimulate nitric oxide (NO) production, whereas IFN-gamma combined with LPS synergisti cally induced iNOS. NaSal inhibited both the production of NO and expr ession of iNOS in microglial cells. Synergy between IFN-gamma and LPS was mainly dependent on tumour necrosis factor-alpha (TNF-alpha) secre tion as the increase of the induction of the iNOS by IFN-gamma plus LP S was associated with the increase of TNF-alpha secretion and IFN-gamm a plus EPS-induced TNF-alpha secretion by microglial cells was decreas ed by the treatment with NaSal. These results suggest a possible use o f NaSal in managing inflammation of the central nervous system through inhibition of the iNOS induction.