Effect of pentoxifylline on nitric oxide released by murine macrophages.
The growing knowledge on the pathological role of tumor necrosis factor alpha (TNF-alpha) and nitric oxide in septic shock stimulated efforts to control their generation pharmacologically in clinical situations. Pentoxifylline (PTXF) is well known as an inhibitor of TNF synthesis, whereas information about its role in suppression of NO generation is much less available. In our study, we have shown that PTXF suppresses the synthesis of both mediators, TNF and NO, released by macrophages activated with different stimuli. However, in contrast to N-monomethyl-L-arginine (an inhibitor of NO synthase), PTXF influenced NO generation only during the induction phase. In conclusion, we suggest that a possible new therapeutic approach in septic shock may result from the inhibition of these two major mediators by simultaneous application of PTXF and a specific inhibitor of NO generation. Further experimental investigations and clinical trials are necessary to evaluate the safety and effectiveness of application of these inhibitors.
Lauterbach
R
R
Department of Immunology, Jagiellonian University, Collegium Medicum, Cracow, Poland.
Grabowska
A
A
Marcinkiewicz
J
J
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D004731:Endotoxins / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008808:Mice, Inbred CBA; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase; D010431:Pentoxifylline / Q000494:pharmacology*; D013212:Staphylococcus epidermidis / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D019323:omega-N-Methylarginine
D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D007371:Interferon-gamma; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D010431:Pentoxifylline