RAPID INDUCTION OF MESSENGER-RNA FOR NITRIC-OXIDE SYNTHASE-II IN RAT NEUTROPHILS IN-VIVO BY ENDOTOXIN AND ITS SUPPRESSION BY PREDNISOLONE

Nitric oxide is believed to participate in nonspecific cellular immuni ty. Gram negative bacterial endotoxins increase the production of reac tive nitrogen intermediates (RNI) in phagocytic cells by inducing the enzyme nitric oxide synthase II (NOS II). Anti-inflammatory glucocorti coids attenuate endotoxin-induced increases in RNI. This study evaluat ed the effect of in vivo administration of prednisolone on Escherichia coli lipopolysaccharide endotoxin (LPS)-induced increases in plasma R NI and neutrophil mRNA for NOS II and production of RNI in the rat. We show that LPS rapidly induces mRNA for NOS II and production of RNI ( NO2- and NO3- anion) in rat neutrophils within 2 hr after in vivo admi nistration of a sublethal dose of 0.5 mg/kg, iv. A pharmacologic dose of prednisolone (50 mu g/kg, im) given 15 min before LPS attenuated pr oduction of NO2- and NO3- by neutrophils and suppressed LPS-stimulated mRNA for NOS II. 3-Amino, 1,2,4-triazine inhibited NO2- and NO3- prod uction without affecting gene expression for NOS II. These data demons trate that LPS rapidly induces functional gene expression for NOS II a nd prednisolone prevents induction of NOS II activity by inhibiting tr anscription of its mRNA.