Effect of nitric oxide releasing paracetamol and flurbiprofen on cytokine production in human blood.
Exposure of anti-coagulated human blood to Escherichia coli lipopolysaccharide (50 ng/ml) resulted in the time-dependent (maximum at 5 h) biosynthesis of interleukin-1beta and tumour necrosis factor-alpha (TNF-alpha). Preincubation with nitroparacetamol or nitroflurbiprofen (but not paracetamol or flurbiprofen) caused dose-related inhibition of the formation of interleukin 1 beta (IC(50)s, 44.5 and 362 microM, n=12) and tumour necrosis factor-alpha (IC(50)s, 9.0 and 0.0009 microM, n=12). The inhibitory effect of nitroparacetamol was completely reversed by (2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; 2-(4-carboxyphenyl)-4,5-dihydro-4,4,5,5-tetramethyl-1H-imidazol-1-yloxy-3-oxide potassium (carboxy-PTIO, 100 microM; NO scavenging agent). Neither the nuclear factor-kappaB transduction inhibitor, pyrrolidinedithiocarbamate (10-1000 microM) nor the nitric oxide donor, 1-hydroxy-2-oxo-3-(3-aminopropyl)-3-isopropyl-1-triazene (NOC-5, 10-1000 microM), affected cytokine formation in these experiments.
Marshall
Melanie
M
Department of Pharmacology, King's College, University of London, Guys' Site, Hodgkin Building, London SE1 9RT, UK.
Moore
Philip K
PK
D000082:Acetaminophen / Q000031:analogs & derivatives / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood*; D005480:Flurbiprofen / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D009566:Nitrates / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology*
D016207:Cytokines; D016166:Free Radical Scavengers; D009566:Nitrates; D020030:Nitric Oxide Donors; C095631:nitroflurbiprofen; D000082:Acetaminophen; D005480:Flurbiprofen; C478738:4-(nitroxy)butanoic acid 4-acetylaminophenyl ester